U.S. BRAND NAMES — Mytelase®
PHARMACOLOGIC CATEGORY
Cholinergic Agonist
DOSING: ADULTS — Myasthenia gravis: Oral: 5-25 mg 3-4 times/day
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Caplet, as chloride [scored]:
Mytelase®: 10 mg
DOSAGE FORMS: CONCISE
Caplet [scored]:
Mytelase®: 10 mg
GENERIC EQUIVALENT AVAILABLE — No
USE — Treatment of myasthenia gravis
ADVERSE REACTIONS SIGNIFICANT — Frequency not defined.
Cardiovascular: Arrhythmias (especially bradycardia), hypotension, carbon monoxide decreased, tachycardia, AV block, nodal rhythm, ECG changes (nonspecific), cardiac arrest, syncope, flushing
Central nervous system: Convulsions, dysarthria, dysphonia, dizziness, loss of consciousness, drowsiness, headache
Dermatologic: Skin rash, thrombophlebitis (I.V.), urticaria
Gastrointestinal: Hyperperistalsis, nausea, vomiting, salivation, diarrhea, stomach cramps, dysphagia, flatulence
Genitourinary: Urinary urgency
Neuromuscular & skeletal: Weakness, fasciculations, muscle cramps, spasms, arthralgia
Ocular: Small pupils, lacrimation
Respiratory: Bronchial secretions increased, laryngospasm, bronchiolar constriction, respiratory muscle paralysis, dyspnea, respiratory depression, respiratory arrest, bronchospasm
Miscellaneous: Diaphoresis increased, anaphylaxis, allergic reactions
CONTRAINDICATIONS — Routine administration of atropine or other belladonna alkaloids with ambenonium is contraindicated because they may suppress the muscarinic symptoms of excessive gastrointestinal stimulation, leaving only the more serious symptoms of muscle fasciculations and paralysis as signs of overdosage; should not be administered to patients receiving mecamylamine
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Anticholinergic insensitivity: May develop for brief or prolonged periods; reduce or withhold dosages until the patient becomes sensitive again. May require respiratory support.
Disease-related concerns: Asthma: Use with caution in patients with asthma. Bradycardia: Use with caution in patients with bradycardia. Hyperthyroidism: Use with caution in patients with hyperthyroidism. Parkinson's disease: Use with caution in patients with Parkinson's disease. Peptic ulcer disease: Use with caution in patients with peptic ulcer disease. Seizures: Use with caution in patients with a history of seizures. Urinary tract obstruction: Use with caution in patients with urinary obstruction.
Special populations: Pediatrics: Safety and efficacy have not been established in children.
Other warnings/precautions: Appropriate use: Differentiation of cholinergic/myasthenia crisis is critical; use edrophonium and clinical judgment. Prolonged action after cholinergics; drug should be discontinued until the patient is stabilized.
DRUG INTERACTIONS
Acetylcholinesterase Inhibitors: May enhance the adverse/toxic effect of Cholinergic Agonists. Risk C: Monitor therapy
PREGNANCY RISK FACTOR — C (show table)
LACTATION — Excretion in breast milk unknown/not recommended
PRICING — (data from drugstore.com)
Tablets (Mytelase)
10 mg (100): $172.65
CANADIAN BRAND NAMES — Mytelase®
INTERNATIONAL BRAND NAMES — Mytelase (FI, HU, PL); Mytelase Chloride (BE, CZ, FR, HN, SE)
Wednesday, June 16, 2010
Ambenonium
U.S. BRAND NAMES — Mytelase®
PHARMACOLOGIC CATEGORY
Cholinergic Agonist
DOSING: ADULTS — Myasthenia gravis: Oral: 5-25 mg 3-4 times/day
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Caplet, as chloride [scored]:
Mytelase®: 10 mg
DOSAGE FORMS: CONCISE
Caplet [scored]:
Mytelase®: 10 mg
GENERIC EQUIVALENT AVAILABLE — No
USE — Treatment of myasthenia gravis
ADVERSE REACTIONS SIGNIFICANT — Frequency not defined.
Cardiovascular: Arrhythmias (especially bradycardia), hypotension, carbon monoxide decreased, tachycardia, AV block, nodal rhythm, ECG changes (nonspecific), cardiac arrest, syncope, flushing
Central nervous system: Convulsions, dysarthria, dysphonia, dizziness, loss of consciousness, drowsiness, headache
Dermatologic: Skin rash, thrombophlebitis (I.V.), urticaria
Gastrointestinal: Hyperperistalsis, nausea, vomiting, salivation, diarrhea, stomach cramps, dysphagia, flatulence
Genitourinary: Urinary urgency
Neuromuscular & skeletal: Weakness, fasciculations, muscle cramps, spasms, arthralgia
Ocular: Small pupils, lacrimation
Respiratory: Bronchial secretions increased, laryngospasm, bronchiolar constriction, respiratory muscle paralysis, dyspnea, respiratory depression, respiratory arrest, bronchospasm
Miscellaneous: Diaphoresis increased, anaphylaxis, allergic reactions
CONTRAINDICATIONS — Routine administration of atropine or other belladonna alkaloids with ambenonium is contraindicated because they may suppress the muscarinic symptoms of excessive gastrointestinal stimulation, leaving only the more serious symptoms of muscle fasciculations and paralysis as signs of overdosage; should not be administered to patients receiving mecamylamine
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Anticholinergic insensitivity: May develop for brief or prolonged periods; reduce or withhold dosages until the patient becomes sensitive again. May require respiratory support.
Disease-related concerns: Asthma: Use with caution in patients with asthma. Bradycardia: Use with caution in patients with bradycardia. Hyperthyroidism: Use with caution in patients with hyperthyroidism. Parkinson's disease: Use with caution in patients with Parkinson's disease. Peptic ulcer disease: Use with caution in patients with peptic ulcer disease. Seizures: Use with caution in patients with a history of seizures. Urinary tract obstruction: Use with caution in patients with urinary obstruction.
Special populations: Pediatrics: Safety and efficacy have not been established in children.
Other warnings/precautions: Appropriate use: Differentiation of cholinergic/myasthenia crisis is critical; use edrophonium and clinical judgment. Prolonged action after cholinergics; drug should be discontinued until the patient is stabilized.
DRUG INTERACTIONS
Acetylcholinesterase Inhibitors: May enhance the adverse/toxic effect of Cholinergic Agonists. Risk C: Monitor therapy
PREGNANCY RISK FACTOR — C (show table)
LACTATION — Excretion in breast milk unknown/not recommended
PRICING — (data from drugstore.com)
Tablets (Mytelase)
10 mg (100): $172.65
CANADIAN BRAND NAMES — Mytelase®
INTERNATIONAL BRAND NAMES — Mytelase (FI, HU, PL); Mytelase Chloride (BE, CZ, FR, HN, SE)
PHARMACOLOGIC CATEGORY
Cholinergic Agonist
DOSING: ADULTS — Myasthenia gravis: Oral: 5-25 mg 3-4 times/day
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Caplet, as chloride [scored]:
Mytelase®: 10 mg
DOSAGE FORMS: CONCISE
Caplet [scored]:
Mytelase®: 10 mg
GENERIC EQUIVALENT AVAILABLE — No
USE — Treatment of myasthenia gravis
ADVERSE REACTIONS SIGNIFICANT — Frequency not defined.
Cardiovascular: Arrhythmias (especially bradycardia), hypotension, carbon monoxide decreased, tachycardia, AV block, nodal rhythm, ECG changes (nonspecific), cardiac arrest, syncope, flushing
Central nervous system: Convulsions, dysarthria, dysphonia, dizziness, loss of consciousness, drowsiness, headache
Dermatologic: Skin rash, thrombophlebitis (I.V.), urticaria
Gastrointestinal: Hyperperistalsis, nausea, vomiting, salivation, diarrhea, stomach cramps, dysphagia, flatulence
Genitourinary: Urinary urgency
Neuromuscular & skeletal: Weakness, fasciculations, muscle cramps, spasms, arthralgia
Ocular: Small pupils, lacrimation
Respiratory: Bronchial secretions increased, laryngospasm, bronchiolar constriction, respiratory muscle paralysis, dyspnea, respiratory depression, respiratory arrest, bronchospasm
Miscellaneous: Diaphoresis increased, anaphylaxis, allergic reactions
CONTRAINDICATIONS — Routine administration of atropine or other belladonna alkaloids with ambenonium is contraindicated because they may suppress the muscarinic symptoms of excessive gastrointestinal stimulation, leaving only the more serious symptoms of muscle fasciculations and paralysis as signs of overdosage; should not be administered to patients receiving mecamylamine
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Anticholinergic insensitivity: May develop for brief or prolonged periods; reduce or withhold dosages until the patient becomes sensitive again. May require respiratory support.
Disease-related concerns: Asthma: Use with caution in patients with asthma. Bradycardia: Use with caution in patients with bradycardia. Hyperthyroidism: Use with caution in patients with hyperthyroidism. Parkinson's disease: Use with caution in patients with Parkinson's disease. Peptic ulcer disease: Use with caution in patients with peptic ulcer disease. Seizures: Use with caution in patients with a history of seizures. Urinary tract obstruction: Use with caution in patients with urinary obstruction.
Special populations: Pediatrics: Safety and efficacy have not been established in children.
Other warnings/precautions: Appropriate use: Differentiation of cholinergic/myasthenia crisis is critical; use edrophonium and clinical judgment. Prolonged action after cholinergics; drug should be discontinued until the patient is stabilized.
DRUG INTERACTIONS
Acetylcholinesterase Inhibitors: May enhance the adverse/toxic effect of Cholinergic Agonists. Risk C: Monitor therapy
PREGNANCY RISK FACTOR — C (show table)
LACTATION — Excretion in breast milk unknown/not recommended
PRICING — (data from drugstore.com)
Tablets (Mytelase)
10 mg (100): $172.65
CANADIAN BRAND NAMES — Mytelase®
INTERNATIONAL BRAND NAMES — Mytelase (FI, HU, PL); Mytelase Chloride (BE, CZ, FR, HN, SE)
Amantadine
MEDICATION SAFETY ISSUES
Sound-alike/look-alike issues:
Amantadine may be confused with ranitidine, rimantadine
Symmetrel® may be confused with Synthroid®
International issues:
Symmetrel® may be confused with Somatrel® which is a brand name for somatorelin in Denmark
SPECIAL ALERTS
CDC Updated Interim Recommendations for the Use of Antivirals During 2009-2010 Influenza Season - September 2009
The Centers for Disease Control and Prevention (CDC) has issued interim recommendations for the use of antivirals for the treatment and prevention of influenza during the 2009-2010 season. These recommendations apply to seasonal influenza and the 2009 H1N1 influenza (formerly known as novel influenza A [H1N1]). Antiviral doses and schedules for treatment or chemoprophylaxis of 2009 H1N1 influenza are the same as those recommended for seasonal influenza. Additionally, the U.S. Food and Drug Administration (FDA) has issued a temporary Emergency Use Authorization to allow the use of oseltamivir in children <1 year of age. The following is a summary of the updated interim recommendations:
(1) Treatment with oseltamivir or zanamivir is recommended in any patient hospitalized with suspected or confirmed influenza.
(2) Treatment with oseltamivir or zanamivir is generally recommended for patients who are at higher risk for influenza-related complications (eg, children <5 years of age, adults ≥ 65 years of age, pregnant women, immunosuppressed patients, patients <19 years of age receiving long-term aspirin therapy, and persons with chronic health conditions such as pulmonary, cardiovascular, renal, hepatic, hematologic, neurologic, neuromuscular, or metabolic disorders).
(3) Any suspected influenza patient with warning signs/symptoms (eg, dyspnea, tachypnea, unexplained oxygen desaturation) consistent with an acute lower respiratory tract illness should promptly receive empiric antiviral therapy.
(4) Treatment, when indicated, should be started without delay (within 48 hours of illness onset) and should not await laboratory confirmation. Early initiation is more likely to provide benefit.
(5) Treatment or prophylaxis is generally not required in patients with suspected influenza who present with uncomplicated febrile illness or are not at higher risk for complications.
(6) Postexposure antiviral chemoprophylaxis with oseltamivir or zanamivir may be considered in the following populations after an exposure or close contact of a person with suspected, probable, or confirmed influenza during that person's infectious period ("infectious period" is defined as 1 day before through 24 hours after fever ends):
- Persons at higher risk of influenza complications
- Healthcare and public health workers or first responders
(7) Chemoprophylaxis is generally not recommended if more than 48 hours has lapsed since last exposure to the infectious person, and is not indicated if the exposure did not occur during the infectious period. Chemoprophylaxis is not recommended in healthy children or adults after a potential exposure in the community, school, camp, or other setting.
(8) Currently circulating 2009 H1N1 viruses are susceptible to oseltamivir and zanamivir, but resistant to amantadine and rimantadine. Oseltamivir-resistant 2009 H1N1 viruses have been identified, most commonly observed during chemoprophylaxis or in immunocompromised patients receiving treatment for influenza. Conversely, regular seasonal influenza A (H1N1) is commonly resistant to oseltamivir, but is typically susceptible to rimantadine and amantadine. However, at present, oseltamivir or zanamivir is appropriate for the treatment of seasonal H1N1 influenza. If oseltamivir-resistant seasonal H1N1 viruses become more common or are identified in community outbreaks, zanamivir (or a combination of oseltamivir and rimantadine or amantadine) should be considered for empiric treatment of suspected oseltamivir-resistant seasonal human influenza A (H1N1) virus infection.
CDC recommendations are changing frequently as more information on antiviral susceptibilities and effectiveness becomes available. For the most recent recommendations and information from the CDC, please refer to:
http://www.cdc.gov/h1n1flu/recommendations.htm
http://www.cdc.gov/h1n1flu/guidance/
U.S. BRAND NAMES — Symmetrel®
PHARMACOLOGIC CATEGORY
Anti-Parkinson's Agent, Dopamine Agonist
Antiviral Agent
Antiviral Agent, Adamantane
DOSING: ADULTS
Influenza A treatment/prophylaxis:Note: Due to issues of resistance, amantadine is no longer recommended for the treatment or prophylaxis of influenza A. Please refer to the current ACIP recommendations. The following is based on the manufacturer's labeling:
Influenza A treatment: Oral: 200 mg once daily or 100 mg twice daily (may be preferred to reduce CNS effects); Note: Initiate within 24-48 hours after onset of symptoms; continue for 24-48 hours after symptom resolution (duration of therapy is generally 3-5 days).
Influenza A prophylaxis: Oral: 200 mg once daily or 100 mg twice daily (may be preferred to reduce CNS effects). Note: Continue prophylaxis throughout the peak influenza activity in the community or throughout the entire influenza season in patients who cannot be vaccinated. Development of immunity following vaccination takes ~2 weeks; amantadine therapy should be considered for high-risk patients from the time of vaccination until immunity has developed.
Drug-induced extrapyramidal symptoms: Oral: 100 mg twice daily; may increase to 300 mg/day in divided doses, if needed
Parkinson's disease: Oral: Usual dose: 100 mg twice daily as monotherapy; may increase to 400 mg/day in divided doses, if needed, with close monitoring. Note: Patients with a serious concomitant illness or those receiving high doses of other anti-parkinson drugs should be started at 100 mg/day; may increase to 100 mg twice daily, if needed, after one to several weeks.
DOSING: PEDIATRIC
(For additional information see "Amantadine: Pediatric drug information")
Influenza A treatment/prophylaxis: Oral: Note: Due to issues of resistance, amantadine is no longer recommended for the treatment or prophylaxis of influenza A. Please refer to the current ACIP recommendations. The following is based on the manufacturer's labeling and past ACIP dosing recommendations:
Influenza A treatment:
1-9 years: 5 mg/kg/day in 2 divided doses (manufacturers range: 4.4-8.8 mg/kg/day); maximum dose: 150 mg/day
≥ 10 years and <40 kg: 5 mg/kg/day in 2 divided doses; maximum dose: 150 mg/day (CDC, 2003)
≥ 10 years and ≥ 40 kg: 100 mg twice daily (CDC, 2003)
Note: Initiate within 24-48 hours after onset of symptoms; continue for 24-48 hours after symptom resolution (duration of therapy is generally 3-5 days)
Influenza A prophylaxis: Refer to "Influenza A treatment" dosing. Note: Continue prophylaxis throughout the peak influenza activity in the community or throughout the entire influenza season in patients who cannot be vaccinated. Development of immunity following vaccination takes ~2 weeks; amantadine therapy should be considered for high-risk patients from the time of vaccination until immunity has developed. For children <9 years receiving influenza vaccine for the first time, amantadine prophylaxis should continue for 6 weeks (4 weeks after the first dose and 2 weeks after the second dose).
DOSING: ELDERLY — Patients ≥ 65 years: Adjust dose based on renal function; some patients tolerate the drug better when it is given in 2 divided daily doses (to avoid adverse neurologic reactions).
Influenza A treatment/prophylaxis: 100 mg once daily
DOSING: RENAL IMPAIRMENT
Clcr 30-50 mL/minute: Administer 200 mg on day 1, then 100 mg/day
Clcr 15-29 mL/minute: Administer 200 mg on day 1, then 100 mg on alternate days
Clcr <15 mL/minute: Administer 200 mg every 7 days
Hemodialysis: Administer 200 mg every 7 days
Peritoneal dialysis: No supplemental dose is needed
Continuous arteriovenous or venous-venous hemofiltration: No supplemental dose is needed
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, as hydrochloride: 100 mg
Capsule, softgel, as hydrochloride: 100 mg
Solution, oral, as hydrochloride: 50 mg/5 mL (473 mL)
Syrup, oral, as hydrochloride: 50 mg/5 mL (10 mL, 480 mL)
Tablet, as hydrochloride: 100 mg
Symmetrel®: 100 mg
DOSAGE FORMS: CONCISE
Capsule: 100 mg
Capsule, softgel: 100 mg
Solution, oral: 50 mg/5 mL
Syrup, oral: 50 mg/5 mL
Tablet: 100 mg
Symmetrel®: 100 mg
GENERIC EQUIVALENT AVAILABLE — Yes
USE — Prophylaxis and treatment of influenza A viral infection (per manufacturer labeling; also refer to current ACIP guidelines for recommendations during current flu season); treatment of parkinsonism; treatment of drug-induced extrapyramidal symptoms
Note: In certain circumstances, the ACIP recommends use of amantadine in combination with oseltamivir for the treatment or prophylaxis of influenza A infection when resistance to oseltamivir is suspected.
ADVERSE REACTIONS SIGNIFICANT
1% to 10%:
Cardiovascular: Orthostatic hypotension, peripheral edema
Central nervous system: Agitation, anxiety, ataxia, confusion, delirium, depression, dizziness, dream abnormality, fatigue, hallucinations, headache, insomnia, irritability, lightheadedness, nervousness, somnolence
Dermatologic: Livedo reticularis
Gastrointestinal: Anorexia, constipation, diarrhea, nausea, xerostomia
Respiratory: Dry nose
<1% (Limited to important or life-threatening): Aggressive behavior, agranulocytosis, alkaline phosphatase increased, allergic reaction, ALT increased, AST increased, amnesia, anaphylaxis, arrhythmia, bilirubin increased, BUN increased, cardiac arrest, coma, CPK increased, creatinine increased, delusions, diaphoresis, dysphagia, dyspnea, eczematoid dermatitis, euphoria, GGT increased, heart failure, hyperkinesis, LDH increased, leukopenia, mania, neutropenia, neuroleptic malignant syndrome (NMS; associated with dosage reduction or abrupt withdrawal of amantadine), oculogyric episodes, paresthesia, photosensitivity, psychosis, pulmonary edema, rash, respiratory failure (acute), seizures, suicidal ideation, suicide, urinary retention, withdrawal reactions (may include delirium, hallucinations, and psychosis), visual disturbances
Reported with dopamine agonists: Impulsive/compulsive behaviors (eg, pathological gambling, hypersexuality, binge eating)
CONTRAINDICATIONS — Hypersensitivity to amantadine or any component of the formulation
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving). Impulse control disorders: Dopamine agonists used for Parkinson's disease or restless legs syndrome have been associated with compulsive behaviors and/or loss of impulse control, which has manifested as pathological gambling, libido increases (hypersexuality), and/or binge eating. Causality has not been established, and controversy exists as to whether this phenomenon is related to the underlying disease, prior behaviors/addictions and/or drug therapy. Dose reduction or discontinuation of therapy has been reported to reverse these behaviors in some, but not all cases. Melanoma: Risk for melanoma development is increased in Parkinson's disease patients; drug causation or factors contributing to risk have not been established. Patients should be monitored closely and periodic skin examinations should be performed. Neuroleptic malignant syndrome: Has been associated with neuroleptic malignant syndrome (associated with dose reduction or abrupt discontinuation). Suicidal ideation: There have been reports of suicidal ideation/attempt in patients with and without a history of psychiatric illness. May exacerbate mental problems in patients with a history of mental illness.
Disease-related concerns: Cardiovascular disease: Use with caution in patients with heart failure, peripheral edema, or orthostatic hypotension; dosage reduction may be required. Eczema: Use with caution in patients with a history of recurrent and eczematoid dermatitis. Glaucoma: Avoid in untreated angle closure glaucoma. Hepatic impairment: Use with caution in patients with hepatic impairment; rarely, elevations in transaminases have been reported. Influenza A: Appropriate use: Consult current guidelines. Due to increased resistance, the ACIP has recommended that rimantadine and amantadine no longer be used for the treatment or prophylaxis of influenza A in the United States until susceptibility has been re-established. Parkinson's disease: Appropriate use: When treating Parkinson's disease, do not discontinue abruptly. In many patients, the therapeutic benefits of amantadine are limited to a few months. Psychosis: Use with caution in patients with uncontrolled psychosis or severe psychoneurosis. Renal impairment: Use with caution in patients with renal impairment; dosage reduction recommended. Seizure disorder: Use with caution in patients with a history of seizure disorder.
Concurrent drug therapy issues: CNS stimulants: Use with caution in patients receiving CNS stimulant drugs.
Special populations: Elderly: Use with caution in the elderly; may be more susceptible to CNS effects (using 2 divided daily doses may minimize this effect). These patients may require dosage reductions based on renal function. Pediatrics: Safety and efficacy have not been established in children <1 year of age.
Other warnings/precautions: Withdrawal syndrome: May cause agitation, anxiety, delirium, delusions, depression, hallucinations, paranoia, parkinsonian crisis, slurred speech, or stupor. Upon discontinuation of amantadine therapy, gradually taper dose.
DRUG INTERACTIONS
Antipsychotics (Atypical): May diminish the therapeutic effect of Anti-Parkinson's Agents (Dopamine Agonist). Risk D: Consider therapy modification
Antipsychotics (Typical): May diminish the therapeutic effect of Anti-Parkinson's Agents (Dopamine Agonist). Risk D: Consider therapy modification
Influenza Virus Vaccine: Antiviral Agents (Influenza A and B) may diminish the therapeutic effect of Influenza Virus Vaccine. This only pertains to live, attentuated influenza virus vaccine. Risk D: Consider therapy modification
MAO Inhibitors: May enhance the orthostatic effect of Orthostasis Producing Agents. Risk C: Monitor therapy
Metoclopramide: May diminish the therapeutic effect of Anti-Parkinson's Agents (Dopamine Agonist). Risk C: Monitor therapy
Trimethoprim: May enhance the adverse/toxic effect of Amantadine. Specifically, the risk of myoclonus and/or delirium may be increased. Amantadine may increase the serum concentration of Trimethoprim. Trimethoprim may increase the serum concentration of Amantadine. Risk C: Monitor therapy
ETHANOL / NUTRITION / HERB INTERACTIONS — Ethanol: Avoid ethanol (may increase CNS adverse effects).
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — Teratogenic effects were observed in animal studies; limited data in humans. Impaired fertility has also been reported during animal studies and during human in vitro fertilization.
LACTATION — Enters breast milk/not recommended
PRICING — (data from drugstore.com)
Capsules (Amantadine HCl)
100 mg (30): $21.99
Syrup (Amantadine HCl)
50 mg/5 mL (120): $15.98
Tablets (Amantadine HCl)
100 mg (30): $33.99
MONITORING PARAMETERS — Renal function, Parkinson's symptoms, mental status, influenza symptoms, blood pressure
CANADIAN BRAND NAMES — Endantadine®; PMS-Amantadine; Symmetrel®
INTERNATIONAL BRAND NAMES — a.m.t. (DE); Amanda (TW); Amandin (TW); Amandine (UY); Amanta (KP); Amantadin (EE); Amantadin-ratiopharm (PL); Amantadina Juventus (ES); Amantadina Llorente (ES); Amantan (BE, LU); Amantix (CO, PL); Amantrel (IN); Amazolon (JP); Atarin (CL, FI); Boidan (JP); Enzil (TW); Hofcomant (AT, FI); Influ (TW); Influ-A (IL); Mantadan (IT); Mantadix (FR, LU); Mantidan (BR); Paritrel (IL); PK-Merz (AE, AT, BF, BG, BH, BJ, CH, CI, CN, CR, CY, CZ, DE, DO, EE, EG, ET, GH, GM, GN, GT, HK, HN, HU, IL, IQ, IR, JO, KE, KP, KW, LB, LR, LU, LY, MA, ML, MR, MU, MW, MX, MY, NE, NG, NI, OM, PA, PK, PT, PY, QA, SA, SC, SD, SL, SN, SV, SY, TN, TW, TZ, UG, YE, ZA, ZM, ZW); Prayanol (CN); Symmetrel (AE, AT, AU, BH, CH, CY, EG, GB, GR, HR, IE, IL, IQ, IR, JO, KW, LB, LY, NL, NO, OM, QA, SA, SY, VE, YE); Viregyt-K (BG, HU, PL); Virofral (DK); Virosol (AR)
MECHANISM OF ACTION — As an antiviral, blocks the uncoating of influenza A virus preventing penetration of virus into host; antiparkinsonian activity may be due to its blocking the reuptake of dopamine into presynaptic neurons or by increasing dopamine release from presynaptic fibers
PHARMACODYNAMICS / KINETICS
Onset of action: Antidyskinetic: Within 48 hours
Absorption: Well absorbed
Distribution: Vd: Normal: 1.5-6.1 L/kg; Renal failure: 5.1 +/- 0.2 L/kg; in saliva, tear film, and nasal secretions; in animals, tissue (especially lung) concentrations higher than serum concentrations; crosses blood-brain barrier
Protein binding: Normal renal function: ~67%; Hemodialysis: ~59%
Metabolism: Not appreciable; small amounts of an acetyl metabolite identified
Bioavailability: 86% to 90%
Half-life elimination: Normal renal function: 16 +/- 6 hours (9-31 hours); Healthy, older (≥ 60 years) males: 29 hours (range: 20-41 hours); End-stage renal disease: 7-10 days
Time to peak, plasma: 2-4 hours
Excretion: Urine (80% to 90% unchanged) by glomerular filtration and tubular secretion
PATIENT INFORMATION — Do not abruptly discontinue therapy; it may precipitate a parkinsonian crisis. May impair ability to perform activities requiring mental alertness or coordination. Take throughout flu season or for at least 10 days following vaccination for effective prophylaxis. Take second dose of the day in early afternoon to decrease incidence of insomnia.
Sound-alike/look-alike issues:
Amantadine may be confused with ranitidine, rimantadine
Symmetrel® may be confused with Synthroid®
International issues:
Symmetrel® may be confused with Somatrel® which is a brand name for somatorelin in Denmark
SPECIAL ALERTS
CDC Updated Interim Recommendations for the Use of Antivirals During 2009-2010 Influenza Season - September 2009
The Centers for Disease Control and Prevention (CDC) has issued interim recommendations for the use of antivirals for the treatment and prevention of influenza during the 2009-2010 season. These recommendations apply to seasonal influenza and the 2009 H1N1 influenza (formerly known as novel influenza A [H1N1]). Antiviral doses and schedules for treatment or chemoprophylaxis of 2009 H1N1 influenza are the same as those recommended for seasonal influenza. Additionally, the U.S. Food and Drug Administration (FDA) has issued a temporary Emergency Use Authorization to allow the use of oseltamivir in children <1 year of age. The following is a summary of the updated interim recommendations:
(1) Treatment with oseltamivir or zanamivir is recommended in any patient hospitalized with suspected or confirmed influenza.
(2) Treatment with oseltamivir or zanamivir is generally recommended for patients who are at higher risk for influenza-related complications (eg, children <5 years of age, adults ≥ 65 years of age, pregnant women, immunosuppressed patients, patients <19 years of age receiving long-term aspirin therapy, and persons with chronic health conditions such as pulmonary, cardiovascular, renal, hepatic, hematologic, neurologic, neuromuscular, or metabolic disorders).
(3) Any suspected influenza patient with warning signs/symptoms (eg, dyspnea, tachypnea, unexplained oxygen desaturation) consistent with an acute lower respiratory tract illness should promptly receive empiric antiviral therapy.
(4) Treatment, when indicated, should be started without delay (within 48 hours of illness onset) and should not await laboratory confirmation. Early initiation is more likely to provide benefit.
(5) Treatment or prophylaxis is generally not required in patients with suspected influenza who present with uncomplicated febrile illness or are not at higher risk for complications.
(6) Postexposure antiviral chemoprophylaxis with oseltamivir or zanamivir may be considered in the following populations after an exposure or close contact of a person with suspected, probable, or confirmed influenza during that person's infectious period ("infectious period" is defined as 1 day before through 24 hours after fever ends):
- Persons at higher risk of influenza complications
- Healthcare and public health workers or first responders
(7) Chemoprophylaxis is generally not recommended if more than 48 hours has lapsed since last exposure to the infectious person, and is not indicated if the exposure did not occur during the infectious period. Chemoprophylaxis is not recommended in healthy children or adults after a potential exposure in the community, school, camp, or other setting.
(8) Currently circulating 2009 H1N1 viruses are susceptible to oseltamivir and zanamivir, but resistant to amantadine and rimantadine. Oseltamivir-resistant 2009 H1N1 viruses have been identified, most commonly observed during chemoprophylaxis or in immunocompromised patients receiving treatment for influenza. Conversely, regular seasonal influenza A (H1N1) is commonly resistant to oseltamivir, but is typically susceptible to rimantadine and amantadine. However, at present, oseltamivir or zanamivir is appropriate for the treatment of seasonal H1N1 influenza. If oseltamivir-resistant seasonal H1N1 viruses become more common or are identified in community outbreaks, zanamivir (or a combination of oseltamivir and rimantadine or amantadine) should be considered for empiric treatment of suspected oseltamivir-resistant seasonal human influenza A (H1N1) virus infection.
CDC recommendations are changing frequently as more information on antiviral susceptibilities and effectiveness becomes available. For the most recent recommendations and information from the CDC, please refer to:
http://www.cdc.gov/h1n1flu/recommendations.htm
http://www.cdc.gov/h1n1flu/guidance/
U.S. BRAND NAMES — Symmetrel®
PHARMACOLOGIC CATEGORY
Anti-Parkinson's Agent, Dopamine Agonist
Antiviral Agent
Antiviral Agent, Adamantane
DOSING: ADULTS
Influenza A treatment/prophylaxis:Note: Due to issues of resistance, amantadine is no longer recommended for the treatment or prophylaxis of influenza A. Please refer to the current ACIP recommendations. The following is based on the manufacturer's labeling:
Influenza A treatment: Oral: 200 mg once daily or 100 mg twice daily (may be preferred to reduce CNS effects); Note: Initiate within 24-48 hours after onset of symptoms; continue for 24-48 hours after symptom resolution (duration of therapy is generally 3-5 days).
Influenza A prophylaxis: Oral: 200 mg once daily or 100 mg twice daily (may be preferred to reduce CNS effects). Note: Continue prophylaxis throughout the peak influenza activity in the community or throughout the entire influenza season in patients who cannot be vaccinated. Development of immunity following vaccination takes ~2 weeks; amantadine therapy should be considered for high-risk patients from the time of vaccination until immunity has developed.
Drug-induced extrapyramidal symptoms: Oral: 100 mg twice daily; may increase to 300 mg/day in divided doses, if needed
Parkinson's disease: Oral: Usual dose: 100 mg twice daily as monotherapy; may increase to 400 mg/day in divided doses, if needed, with close monitoring. Note: Patients with a serious concomitant illness or those receiving high doses of other anti-parkinson drugs should be started at 100 mg/day; may increase to 100 mg twice daily, if needed, after one to several weeks.
DOSING: PEDIATRIC
(For additional information see "Amantadine: Pediatric drug information")
Influenza A treatment/prophylaxis: Oral: Note: Due to issues of resistance, amantadine is no longer recommended for the treatment or prophylaxis of influenza A. Please refer to the current ACIP recommendations. The following is based on the manufacturer's labeling and past ACIP dosing recommendations:
Influenza A treatment:
1-9 years: 5 mg/kg/day in 2 divided doses (manufacturers range: 4.4-8.8 mg/kg/day); maximum dose: 150 mg/day
≥ 10 years and <40 kg: 5 mg/kg/day in 2 divided doses; maximum dose: 150 mg/day (CDC, 2003)
≥ 10 years and ≥ 40 kg: 100 mg twice daily (CDC, 2003)
Note: Initiate within 24-48 hours after onset of symptoms; continue for 24-48 hours after symptom resolution (duration of therapy is generally 3-5 days)
Influenza A prophylaxis: Refer to "Influenza A treatment" dosing. Note: Continue prophylaxis throughout the peak influenza activity in the community or throughout the entire influenza season in patients who cannot be vaccinated. Development of immunity following vaccination takes ~2 weeks; amantadine therapy should be considered for high-risk patients from the time of vaccination until immunity has developed. For children <9 years receiving influenza vaccine for the first time, amantadine prophylaxis should continue for 6 weeks (4 weeks after the first dose and 2 weeks after the second dose).
DOSING: ELDERLY — Patients ≥ 65 years: Adjust dose based on renal function; some patients tolerate the drug better when it is given in 2 divided daily doses (to avoid adverse neurologic reactions).
Influenza A treatment/prophylaxis: 100 mg once daily
DOSING: RENAL IMPAIRMENT
Clcr 30-50 mL/minute: Administer 200 mg on day 1, then 100 mg/day
Clcr 15-29 mL/minute: Administer 200 mg on day 1, then 100 mg on alternate days
Clcr <15 mL/minute: Administer 200 mg every 7 days
Hemodialysis: Administer 200 mg every 7 days
Peritoneal dialysis: No supplemental dose is needed
Continuous arteriovenous or venous-venous hemofiltration: No supplemental dose is needed
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, as hydrochloride: 100 mg
Capsule, softgel, as hydrochloride: 100 mg
Solution, oral, as hydrochloride: 50 mg/5 mL (473 mL)
Syrup, oral, as hydrochloride: 50 mg/5 mL (10 mL, 480 mL)
Tablet, as hydrochloride: 100 mg
Symmetrel®: 100 mg
DOSAGE FORMS: CONCISE
Capsule: 100 mg
Capsule, softgel: 100 mg
Solution, oral: 50 mg/5 mL
Syrup, oral: 50 mg/5 mL
Tablet: 100 mg
Symmetrel®: 100 mg
GENERIC EQUIVALENT AVAILABLE — Yes
USE — Prophylaxis and treatment of influenza A viral infection (per manufacturer labeling; also refer to current ACIP guidelines for recommendations during current flu season); treatment of parkinsonism; treatment of drug-induced extrapyramidal symptoms
Note: In certain circumstances, the ACIP recommends use of amantadine in combination with oseltamivir for the treatment or prophylaxis of influenza A infection when resistance to oseltamivir is suspected.
ADVERSE REACTIONS SIGNIFICANT
1% to 10%:
Cardiovascular: Orthostatic hypotension, peripheral edema
Central nervous system: Agitation, anxiety, ataxia, confusion, delirium, depression, dizziness, dream abnormality, fatigue, hallucinations, headache, insomnia, irritability, lightheadedness, nervousness, somnolence
Dermatologic: Livedo reticularis
Gastrointestinal: Anorexia, constipation, diarrhea, nausea, xerostomia
Respiratory: Dry nose
<1% (Limited to important or life-threatening): Aggressive behavior, agranulocytosis, alkaline phosphatase increased, allergic reaction, ALT increased, AST increased, amnesia, anaphylaxis, arrhythmia, bilirubin increased, BUN increased, cardiac arrest, coma, CPK increased, creatinine increased, delusions, diaphoresis, dysphagia, dyspnea, eczematoid dermatitis, euphoria, GGT increased, heart failure, hyperkinesis, LDH increased, leukopenia, mania, neutropenia, neuroleptic malignant syndrome (NMS; associated with dosage reduction or abrupt withdrawal of amantadine), oculogyric episodes, paresthesia, photosensitivity, psychosis, pulmonary edema, rash, respiratory failure (acute), seizures, suicidal ideation, suicide, urinary retention, withdrawal reactions (may include delirium, hallucinations, and psychosis), visual disturbances
Reported with dopamine agonists: Impulsive/compulsive behaviors (eg, pathological gambling, hypersexuality, binge eating)
CONTRAINDICATIONS — Hypersensitivity to amantadine or any component of the formulation
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving). Impulse control disorders: Dopamine agonists used for Parkinson's disease or restless legs syndrome have been associated with compulsive behaviors and/or loss of impulse control, which has manifested as pathological gambling, libido increases (hypersexuality), and/or binge eating. Causality has not been established, and controversy exists as to whether this phenomenon is related to the underlying disease, prior behaviors/addictions and/or drug therapy. Dose reduction or discontinuation of therapy has been reported to reverse these behaviors in some, but not all cases. Melanoma: Risk for melanoma development is increased in Parkinson's disease patients; drug causation or factors contributing to risk have not been established. Patients should be monitored closely and periodic skin examinations should be performed. Neuroleptic malignant syndrome: Has been associated with neuroleptic malignant syndrome (associated with dose reduction or abrupt discontinuation). Suicidal ideation: There have been reports of suicidal ideation/attempt in patients with and without a history of psychiatric illness. May exacerbate mental problems in patients with a history of mental illness.
Disease-related concerns: Cardiovascular disease: Use with caution in patients with heart failure, peripheral edema, or orthostatic hypotension; dosage reduction may be required. Eczema: Use with caution in patients with a history of recurrent and eczematoid dermatitis. Glaucoma: Avoid in untreated angle closure glaucoma. Hepatic impairment: Use with caution in patients with hepatic impairment; rarely, elevations in transaminases have been reported. Influenza A: Appropriate use: Consult current guidelines. Due to increased resistance, the ACIP has recommended that rimantadine and amantadine no longer be used for the treatment or prophylaxis of influenza A in the United States until susceptibility has been re-established. Parkinson's disease: Appropriate use: When treating Parkinson's disease, do not discontinue abruptly. In many patients, the therapeutic benefits of amantadine are limited to a few months. Psychosis: Use with caution in patients with uncontrolled psychosis or severe psychoneurosis. Renal impairment: Use with caution in patients with renal impairment; dosage reduction recommended. Seizure disorder: Use with caution in patients with a history of seizure disorder.
Concurrent drug therapy issues: CNS stimulants: Use with caution in patients receiving CNS stimulant drugs.
Special populations: Elderly: Use with caution in the elderly; may be more susceptible to CNS effects (using 2 divided daily doses may minimize this effect). These patients may require dosage reductions based on renal function. Pediatrics: Safety and efficacy have not been established in children <1 year of age.
Other warnings/precautions: Withdrawal syndrome: May cause agitation, anxiety, delirium, delusions, depression, hallucinations, paranoia, parkinsonian crisis, slurred speech, or stupor. Upon discontinuation of amantadine therapy, gradually taper dose.
DRUG INTERACTIONS
Antipsychotics (Atypical): May diminish the therapeutic effect of Anti-Parkinson's Agents (Dopamine Agonist). Risk D: Consider therapy modification
Antipsychotics (Typical): May diminish the therapeutic effect of Anti-Parkinson's Agents (Dopamine Agonist). Risk D: Consider therapy modification
Influenza Virus Vaccine: Antiviral Agents (Influenza A and B) may diminish the therapeutic effect of Influenza Virus Vaccine. This only pertains to live, attentuated influenza virus vaccine. Risk D: Consider therapy modification
MAO Inhibitors: May enhance the orthostatic effect of Orthostasis Producing Agents. Risk C: Monitor therapy
Metoclopramide: May diminish the therapeutic effect of Anti-Parkinson's Agents (Dopamine Agonist). Risk C: Monitor therapy
Trimethoprim: May enhance the adverse/toxic effect of Amantadine. Specifically, the risk of myoclonus and/or delirium may be increased. Amantadine may increase the serum concentration of Trimethoprim. Trimethoprim may increase the serum concentration of Amantadine. Risk C: Monitor therapy
ETHANOL / NUTRITION / HERB INTERACTIONS — Ethanol: Avoid ethanol (may increase CNS adverse effects).
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — Teratogenic effects were observed in animal studies; limited data in humans. Impaired fertility has also been reported during animal studies and during human in vitro fertilization.
LACTATION — Enters breast milk/not recommended
PRICING — (data from drugstore.com)
Capsules (Amantadine HCl)
100 mg (30): $21.99
Syrup (Amantadine HCl)
50 mg/5 mL (120): $15.98
Tablets (Amantadine HCl)
100 mg (30): $33.99
MONITORING PARAMETERS — Renal function, Parkinson's symptoms, mental status, influenza symptoms, blood pressure
CANADIAN BRAND NAMES — Endantadine®; PMS-Amantadine; Symmetrel®
INTERNATIONAL BRAND NAMES — a.m.t. (DE); Amanda (TW); Amandin (TW); Amandine (UY); Amanta (KP); Amantadin (EE); Amantadin-ratiopharm (PL); Amantadina Juventus (ES); Amantadina Llorente (ES); Amantan (BE, LU); Amantix (CO, PL); Amantrel (IN); Amazolon (JP); Atarin (CL, FI); Boidan (JP); Enzil (TW); Hofcomant (AT, FI); Influ (TW); Influ-A (IL); Mantadan (IT); Mantadix (FR, LU); Mantidan (BR); Paritrel (IL); PK-Merz (AE, AT, BF, BG, BH, BJ, CH, CI, CN, CR, CY, CZ, DE, DO, EE, EG, ET, GH, GM, GN, GT, HK, HN, HU, IL, IQ, IR, JO, KE, KP, KW, LB, LR, LU, LY, MA, ML, MR, MU, MW, MX, MY, NE, NG, NI, OM, PA, PK, PT, PY, QA, SA, SC, SD, SL, SN, SV, SY, TN, TW, TZ, UG, YE, ZA, ZM, ZW); Prayanol (CN); Symmetrel (AE, AT, AU, BH, CH, CY, EG, GB, GR, HR, IE, IL, IQ, IR, JO, KW, LB, LY, NL, NO, OM, QA, SA, SY, VE, YE); Viregyt-K (BG, HU, PL); Virofral (DK); Virosol (AR)
MECHANISM OF ACTION — As an antiviral, blocks the uncoating of influenza A virus preventing penetration of virus into host; antiparkinsonian activity may be due to its blocking the reuptake of dopamine into presynaptic neurons or by increasing dopamine release from presynaptic fibers
PHARMACODYNAMICS / KINETICS
Onset of action: Antidyskinetic: Within 48 hours
Absorption: Well absorbed
Distribution: Vd: Normal: 1.5-6.1 L/kg; Renal failure: 5.1 +/- 0.2 L/kg; in saliva, tear film, and nasal secretions; in animals, tissue (especially lung) concentrations higher than serum concentrations; crosses blood-brain barrier
Protein binding: Normal renal function: ~67%; Hemodialysis: ~59%
Metabolism: Not appreciable; small amounts of an acetyl metabolite identified
Bioavailability: 86% to 90%
Half-life elimination: Normal renal function: 16 +/- 6 hours (9-31 hours); Healthy, older (≥ 60 years) males: 29 hours (range: 20-41 hours); End-stage renal disease: 7-10 days
Time to peak, plasma: 2-4 hours
Excretion: Urine (80% to 90% unchanged) by glomerular filtration and tubular secretion
PATIENT INFORMATION — Do not abruptly discontinue therapy; it may precipitate a parkinsonian crisis. May impair ability to perform activities requiring mental alertness or coordination. Take throughout flu season or for at least 10 days following vaccination for effective prophylaxis. Take second dose of the day in early afternoon to decrease incidence of insomnia.
Alvimopan
MEDICATION SAFETY ISSUES
Sound-alike/look-alike issues:
Alvimopan may be confused with almotriptan
U.S. BRAND NAMES — Entereg®
PHARMACOLOGIC CATEGORY
Gastrointestinal Agent, Miscellaneous
Opioid Antagonist, Peripherally-Acting
DOSING: ADULTS — Note: For hospital use only.
Management of postoperative ileus: Oral:
Initial: 12 mg administered 30 minutes to 5 hours prior to surgery
Maintenance: 12 mg twice daily beginning the day after surgery for a maximum of 7 days or until discharged from hospital (maximum total treatment doses: 15 doses)
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT
Mild-to-severe impairment: No adjustment needed; use caution.
ESRD: Use not recommended.
DOSING: HEPATIC IMPAIRMENT
Mild-to-moderate impairment (Child-Pugh class A and B): No adjustment needed; use caution.
Severe impairment (Child-Pugh class C): Use not recommended.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics ); consult specific product labeling.
Capsule:
Entereg®: 12 mg
DOSAGE FORMS: CONCISE
Capsule:
Entereg®: 12 mg
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Patient must be hospitalized. Initial dose should be administered 30 minutes to 5 hours prior to surgery.
USE — Accelerate the time to upper and lower GI recovery following partial large or small bowel resection surgery with primary anastomosis
ADVERSE REACTIONS SIGNIFICANT — Note: Incidence reported limited to bowel resection patients only. 1% to 10%:
Endocrine & metabolic: Hypokalemia (10%)
Gastrointestinal: Dyspepsia (7%)
Genitourinary: Urinary retention (3%)
Hematologic: Anemia (5%)
Neuromuscular & skeletal: Back pain (3%)
CONTRAINDICATIONS — Patients who have taken therapeutic doses of opioids for more than 7 consecutive days immediately prior to alvimopan
WARNINGS / PRECAUTIONS
Boxed warnings: Appropriate use: See "Other warnings/precautions" below.
Concerns related to adverse effects: Cardiovascular effects: A trend towards an increased incidence of MI was observed in alvimopan (low dose) treated patients compared to placebo in a 12-month study in patients treated with opioids for chronic pain. MI was generally observed more frequently in the initial 1-4 months of treatment. Other studies have not observed this trend and a causal relationship has not been found.
Disease-related concerns: Complete bowel obstruction: Use not recommended in patients undergoing surgery for complete bowel obstruction. Hepatic impairment: Use with caution in patients with mild-to-moderate hepatic impairment (Child-Pugh classes A and B); use not recommended with severe impairment (Child-Pugh class C). Renal impairment: Use with caution in patients with renal impairment; use not recommended in patients with ESRD.
Concurrent drug therapy issues: Opioids: Use with caution in patients recently exposed to opioids; may be more sensitive to gastrointestinal adverse effects (eg, abdominal pain, diarrhea, nausea and vomiting). Contraindicated in patients who have received therapeutic opioids for >7 consecutive days immediately prior to use.
Special populations: Pediatrics: Safety and efficacy have not been established in children.
Other warnings/precautions: Appropriate use: [U.S. Boxed Warning]: For short-term (≤ 15 doses) hospital use only. Only hospitals that have registered through the ENTEREG Access Support and Education (E.A.S.E.™ ) Program and met all requirements may use. It will not be dispensed to patients who have been discharged from the hospital.
RESTRICTIONS — Only hospitals enrolled in the ENTEREG Access Support and Education (E.A.S.E.™ ) Program may administer this medication. Hospital staff must be educated on need to limit to short-term (no more than 15 doses) and inpatient use. Hospitals may contact the E.A.S.E.™ program at 1-866-423-6567 (1-866-4ADOLOR).
METABOLISM / TRANSPORT EFFECTS — Substrate of P-glycoprotein
DRUG INTERACTIONS
Analgesics (Opioid): May enhance the adverse/toxic effect of Alvimopan. This is most notable for patients receiving long-term (i.e., more than 7 days) opiates prior to alvimopan initiation. Management: Alvimopan is contraindicated in patients receiving therapeutic doses of opioids for more than 7 consecutive days immediately prior to alvimopan initiation. Risk D: Consider therapy modification
ETHANOL / NUTRITION / HERB INTERACTIONS — Food: When administered with a high-fat meal, extent and rate of absorption may be reduced (Cmax and AUC decreased by ~38% and 21%, respectively).
PREGNANCY RISK FACTOR — B (show table)
PREGNANCY IMPLICATIONS — Animal studies have not shown teratogenic effects to the fetus. However, there are no adequate and well-controlled studies in pregnant women; use during pregnancy only if clearly needed.
LACTATION — Excretion in breast milk unknown/use caution
DIETARY CONSIDERATIONS — Take with or without food; high-fat meals may decrease the rate and extent of absorption
MECHANISM OF ACTION — An opioid receptor antagonist which blocks opioid binding at the mu receptor; alvimopan has restricted ability to cross the blood-brain barrier at therapeutic doses. It selectively and competitively binds to the GI tract mu opioid receptors and antagonizes the peripheral effects of opioids on gastrointestinal motility and secretion. Does not affect opioid analgesic effects or induce opioid withdrawal symptoms.
PHARMACODYNAMICS / KINETICS
Distribution: Vd: 20-40 L
Protein binding: Parent drug: 80%; metabolite: 94% (both primarily to albumin)
Metabolism: Hydrolyzed to an amide hydrolysis compound (active metabolite) by gut microflora; further metabolism of active metabolite to glucuronide conjugates and other minor metabolites.
Bioavailability: ~6% (range: 1% to 19%)
Half-life elimination: 10-18 hours
Time to peak, plasma: ~2 hours
Excretion: Urine (35% as unchanged drug and metabolites); feces (via biliary excretion)
Sound-alike/look-alike issues:
Alvimopan may be confused with almotriptan
U.S. BRAND NAMES — Entereg®
PHARMACOLOGIC CATEGORY
Gastrointestinal Agent, Miscellaneous
Opioid Antagonist, Peripherally-Acting
DOSING: ADULTS — Note: For hospital use only.
Management of postoperative ileus: Oral:
Initial: 12 mg administered 30 minutes to 5 hours prior to surgery
Maintenance: 12 mg twice daily beginning the day after surgery for a maximum of 7 days or until discharged from hospital (maximum total treatment doses: 15 doses)
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT
Mild-to-severe impairment: No adjustment needed; use caution.
ESRD: Use not recommended.
DOSING: HEPATIC IMPAIRMENT
Mild-to-moderate impairment (Child-Pugh class A and B): No adjustment needed; use caution.
Severe impairment (Child-Pugh class C): Use not recommended.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics ); consult specific product labeling.
Capsule:
Entereg®: 12 mg
DOSAGE FORMS: CONCISE
Capsule:
Entereg®: 12 mg
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Patient must be hospitalized. Initial dose should be administered 30 minutes to 5 hours prior to surgery.
USE — Accelerate the time to upper and lower GI recovery following partial large or small bowel resection surgery with primary anastomosis
ADVERSE REACTIONS SIGNIFICANT — Note: Incidence reported limited to bowel resection patients only. 1% to 10%:
Endocrine & metabolic: Hypokalemia (10%)
Gastrointestinal: Dyspepsia (7%)
Genitourinary: Urinary retention (3%)
Hematologic: Anemia (5%)
Neuromuscular & skeletal: Back pain (3%)
CONTRAINDICATIONS — Patients who have taken therapeutic doses of opioids for more than 7 consecutive days immediately prior to alvimopan
WARNINGS / PRECAUTIONS
Boxed warnings: Appropriate use: See "Other warnings/precautions" below.
Concerns related to adverse effects: Cardiovascular effects: A trend towards an increased incidence of MI was observed in alvimopan (low dose) treated patients compared to placebo in a 12-month study in patients treated with opioids for chronic pain. MI was generally observed more frequently in the initial 1-4 months of treatment. Other studies have not observed this trend and a causal relationship has not been found.
Disease-related concerns: Complete bowel obstruction: Use not recommended in patients undergoing surgery for complete bowel obstruction. Hepatic impairment: Use with caution in patients with mild-to-moderate hepatic impairment (Child-Pugh classes A and B); use not recommended with severe impairment (Child-Pugh class C). Renal impairment: Use with caution in patients with renal impairment; use not recommended in patients with ESRD.
Concurrent drug therapy issues: Opioids: Use with caution in patients recently exposed to opioids; may be more sensitive to gastrointestinal adverse effects (eg, abdominal pain, diarrhea, nausea and vomiting). Contraindicated in patients who have received therapeutic opioids for >7 consecutive days immediately prior to use.
Special populations: Pediatrics: Safety and efficacy have not been established in children.
Other warnings/precautions: Appropriate use: [U.S. Boxed Warning]: For short-term (≤ 15 doses) hospital use only. Only hospitals that have registered through the ENTEREG Access Support and Education (E.A.S.E.™ ) Program and met all requirements may use. It will not be dispensed to patients who have been discharged from the hospital.
RESTRICTIONS — Only hospitals enrolled in the ENTEREG Access Support and Education (E.A.S.E.™ ) Program may administer this medication. Hospital staff must be educated on need to limit to short-term (no more than 15 doses) and inpatient use. Hospitals may contact the E.A.S.E.™ program at 1-866-423-6567 (1-866-4ADOLOR).
METABOLISM / TRANSPORT EFFECTS — Substrate of P-glycoprotein
DRUG INTERACTIONS
Analgesics (Opioid): May enhance the adverse/toxic effect of Alvimopan. This is most notable for patients receiving long-term (i.e., more than 7 days) opiates prior to alvimopan initiation. Management: Alvimopan is contraindicated in patients receiving therapeutic doses of opioids for more than 7 consecutive days immediately prior to alvimopan initiation. Risk D: Consider therapy modification
ETHANOL / NUTRITION / HERB INTERACTIONS — Food: When administered with a high-fat meal, extent and rate of absorption may be reduced (Cmax and AUC decreased by ~38% and 21%, respectively).
PREGNANCY RISK FACTOR — B (show table)
PREGNANCY IMPLICATIONS — Animal studies have not shown teratogenic effects to the fetus. However, there are no adequate and well-controlled studies in pregnant women; use during pregnancy only if clearly needed.
LACTATION — Excretion in breast milk unknown/use caution
DIETARY CONSIDERATIONS — Take with or without food; high-fat meals may decrease the rate and extent of absorption
MECHANISM OF ACTION — An opioid receptor antagonist which blocks opioid binding at the mu receptor; alvimopan has restricted ability to cross the blood-brain barrier at therapeutic doses. It selectively and competitively binds to the GI tract mu opioid receptors and antagonizes the peripheral effects of opioids on gastrointestinal motility and secretion. Does not affect opioid analgesic effects or induce opioid withdrawal symptoms.
PHARMACODYNAMICS / KINETICS
Distribution: Vd: 20-40 L
Protein binding: Parent drug: 80%; metabolite: 94% (both primarily to albumin)
Metabolism: Hydrolyzed to an amide hydrolysis compound (active metabolite) by gut microflora; further metabolism of active metabolite to glucuronide conjugates and other minor metabolites.
Bioavailability: ~6% (range: 1% to 19%)
Half-life elimination: 10-18 hours
Time to peak, plasma: ~2 hours
Excretion: Urine (35% as unchanged drug and metabolites); feces (via biliary excretion)
Amantadine
MEDICATION SAFETY ISSUES
Sound-alike/look-alike issues:
Amantadine may be confused with ranitidine, rimantadine
Symmetrel® may be confused with Synthroid®
International issues:
Symmetrel® may be confused with Somatrel® which is a brand name for somatorelin in Denmark
SPECIAL ALERTS
CDC Updated Interim Recommendations for the Use of Antivirals During 2009-2010 Influenza Season - September 2009
The Centers for Disease Control and Prevention (CDC) has issued interim recommendations for the use of antivirals for the treatment and prevention of influenza during the 2009-2010 season. These recommendations apply to seasonal influenza and the 2009 H1N1 influenza (formerly known as novel influenza A [H1N1]). Antiviral doses and schedules for treatment or chemoprophylaxis of 2009 H1N1 influenza are the same as those recommended for seasonal influenza. Additionally, the U.S. Food and Drug Administration (FDA) has issued a temporary Emergency Use Authorization to allow the use of oseltamivir in children <1 year of age. The following is a summary of the updated interim recommendations:
(1) Treatment with oseltamivir or zanamivir is recommended in any patient hospitalized with suspected or confirmed influenza.
(2) Treatment with oseltamivir or zanamivir is generally recommended for patients who are at higher risk for influenza-related complications (eg, children <5 years of age, adults ≥ 65 years of age, pregnant women, immunosuppressed patients, patients <19 years of age receiving long-term aspirin therapy, and persons with chronic health conditions such as pulmonary, cardiovascular, renal, hepatic, hematologic, neurologic, neuromuscular, or metabolic disorders).
(3) Any suspected influenza patient with warning signs/symptoms (eg, dyspnea, tachypnea, unexplained oxygen desaturation) consistent with an acute lower respiratory tract illness should promptly receive empiric antiviral therapy.
(4) Treatment, when indicated, should be started without delay (within 48 hours of illness onset) and should not await laboratory confirmation. Early initiation is more likely to provide benefit.
(5) Treatment or prophylaxis is generally not required in patients with suspected influenza who present with uncomplicated febrile illness or are not at higher risk for complications.
(6) Postexposure antiviral chemoprophylaxis with oseltamivir or zanamivir may be considered in the following populations after an exposure or close contact of a person with suspected, probable, or confirmed influenza during that person's infectious period ("infectious period" is defined as 1 day before through 24 hours after fever ends):
- Persons at higher risk of influenza complications
- Healthcare and public health workers or first responders
(7) Chemoprophylaxis is generally not recommended if more than 48 hours has lapsed since last exposure to the infectious person, and is not indicated if the exposure did not occur during the infectious period. Chemoprophylaxis is not recommended in healthy children or adults after a potential exposure in the community, school, camp, or other setting.
(8) Currently circulating 2009 H1N1 viruses are susceptible to oseltamivir and zanamivir, but resistant to amantadine and rimantadine. Oseltamivir-resistant 2009 H1N1 viruses have been identified, most commonly observed during chemoprophylaxis or in immunocompromised patients receiving treatment for influenza. Conversely, regular seasonal influenza A (H1N1) is commonly resistant to oseltamivir, but is typically susceptible to rimantadine and amantadine. However, at present, oseltamivir or zanamivir is appropriate for the treatment of seasonal H1N1 influenza. If oseltamivir-resistant seasonal H1N1 viruses become more common or are identified in community outbreaks, zanamivir (or a combination of oseltamivir and rimantadine or amantadine) should be considered for empiric treatment of suspected oseltamivir-resistant seasonal human influenza A (H1N1) virus infection.
CDC recommendations are changing frequently as more information on antiviral susceptibilities and effectiveness becomes available. For the most recent recommendations and information from the CDC, please refer to:
http://www.cdc.gov/h1n1flu/recommendations.htm
http://www.cdc.gov/h1n1flu/guidance/
U.S. BRAND NAMES — Symmetrel®
PHARMACOLOGIC CATEGORY
Anti-Parkinson's Agent, Dopamine Agonist
Antiviral Agent
Antiviral Agent, Adamantane
DOSING: ADULTS
Influenza A treatment/prophylaxis:Note: Due to issues of resistance, amantadine is no longer recommended for the treatment or prophylaxis of influenza A. Please refer to the current ACIP recommendations. The following is based on the manufacturer's labeling:
Influenza A treatment: Oral: 200 mg once daily or 100 mg twice daily (may be preferred to reduce CNS effects); Note: Initiate within 24-48 hours after onset of symptoms; continue for 24-48 hours after symptom resolution (duration of therapy is generally 3-5 days).
Influenza A prophylaxis: Oral: 200 mg once daily or 100 mg twice daily (may be preferred to reduce CNS effects). Note: Continue prophylaxis throughout the peak influenza activity in the community or throughout the entire influenza season in patients who cannot be vaccinated. Development of immunity following vaccination takes ~2 weeks; amantadine therapy should be considered for high-risk patients from the time of vaccination until immunity has developed.
Drug-induced extrapyramidal symptoms: Oral: 100 mg twice daily; may increase to 300 mg/day in divided doses, if needed
Parkinson's disease: Oral: Usual dose: 100 mg twice daily as monotherapy; may increase to 400 mg/day in divided doses, if needed, with close monitoring. Note: Patients with a serious concomitant illness or those receiving high doses of other anti-parkinson drugs should be started at 100 mg/day; may increase to 100 mg twice daily, if needed, after one to several weeks.
DOSING: PEDIATRIC
(For additional information see "Amantadine: Pediatric drug information")
Influenza A treatment/prophylaxis: Oral: Note: Due to issues of resistance, amantadine is no longer recommended for the treatment or prophylaxis of influenza A. Please refer to the current ACIP recommendations. The following is based on the manufacturer's labeling and past ACIP dosing recommendations:
Influenza A treatment:
1-9 years: 5 mg/kg/day in 2 divided doses (manufacturers range: 4.4-8.8 mg/kg/day); maximum dose: 150 mg/day
≥ 10 years and <40 kg: 5 mg/kg/day in 2 divided doses; maximum dose: 150 mg/day (CDC, 2003)
≥ 10 years and ≥ 40 kg: 100 mg twice daily (CDC, 2003)
Note: Initiate within 24-48 hours after onset of symptoms; continue for 24-48 hours after symptom resolution (duration of therapy is generally 3-5 days)
Influenza A prophylaxis: Refer to "Influenza A treatment" dosing. Note: Continue prophylaxis throughout the peak influenza activity in the community or throughout the entire influenza season in patients who cannot be vaccinated. Development of immunity following vaccination takes ~2 weeks; amantadine therapy should be considered for high-risk patients from the time of vaccination until immunity has developed. For children <9 years receiving influenza vaccine for the first time, amantadine prophylaxis should continue for 6 weeks (4 weeks after the first dose and 2 weeks after the second dose).
DOSING: ELDERLY — Patients ≥ 65 years: Adjust dose based on renal function; some patients tolerate the drug better when it is given in 2 divided daily doses (to avoid adverse neurologic reactions).
Influenza A treatment/prophylaxis: 100 mg once daily
DOSING: RENAL IMPAIRMENT
Clcr 30-50 mL/minute: Administer 200 mg on day 1, then 100 mg/day
Clcr 15-29 mL/minute: Administer 200 mg on day 1, then 100 mg on alternate days
Clcr <15 mL/minute: Administer 200 mg every 7 days
Hemodialysis: Administer 200 mg every 7 days
Peritoneal dialysis: No supplemental dose is needed
Continuous arteriovenous or venous-venous hemofiltration: No supplemental dose is needed
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, as hydrochloride: 100 mg
Capsule, softgel, as hydrochloride: 100 mg
Solution, oral, as hydrochloride: 50 mg/5 mL (473 mL)
Syrup, oral, as hydrochloride: 50 mg/5 mL (10 mL, 480 mL)
Tablet, as hydrochloride: 100 mg
Symmetrel®: 100 mg
DOSAGE FORMS: CONCISE
Capsule: 100 mg
Capsule, softgel: 100 mg
Solution, oral: 50 mg/5 mL
Syrup, oral: 50 mg/5 mL
Tablet: 100 mg
Symmetrel®: 100 mg
GENERIC EQUIVALENT AVAILABLE — Yes
USE — Prophylaxis and treatment of influenza A viral infection (per manufacturer labeling; also refer to current ACIP guidelines for recommendations during current flu season); treatment of parkinsonism; treatment of drug-induced extrapyramidal symptoms
Note: In certain circumstances, the ACIP recommends use of amantadine in combination with oseltamivir for the treatment or prophylaxis of influenza A infection when resistance to oseltamivir is suspected.
ADVERSE REACTIONS SIGNIFICANT
1% to 10%:
Cardiovascular: Orthostatic hypotension, peripheral edema
Central nervous system: Agitation, anxiety, ataxia, confusion, delirium, depression, dizziness, dream abnormality, fatigue, hallucinations, headache, insomnia, irritability, lightheadedness, nervousness, somnolence
Dermatologic: Livedo reticularis
Gastrointestinal: Anorexia, constipation, diarrhea, nausea, xerostomia
Respiratory: Dry nose
<1% (Limited to important or life-threatening): Aggressive behavior, agranulocytosis, alkaline phosphatase increased, allergic reaction, ALT increased, AST increased, amnesia, anaphylaxis, arrhythmia, bilirubin increased, BUN increased, cardiac arrest, coma, CPK increased, creatinine increased, delusions, diaphoresis, dysphagia, dyspnea, eczematoid dermatitis, euphoria, GGT increased, heart failure, hyperkinesis, LDH increased, leukopenia, mania, neutropenia, neuroleptic malignant syndrome (NMS; associated with dosage reduction or abrupt withdrawal of amantadine), oculogyric episodes, paresthesia, photosensitivity, psychosis, pulmonary edema, rash, respiratory failure (acute), seizures, suicidal ideation, suicide, urinary retention, withdrawal reactions (may include delirium, hallucinations, and psychosis), visual disturbances
Reported with dopamine agonists: Impulsive/compulsive behaviors (eg, pathological gambling, hypersexuality, binge eating)
CONTRAINDICATIONS — Hypersensitivity to amantadine or any component of the formulation
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving). Impulse control disorders: Dopamine agonists used for Parkinson's disease or restless legs syndrome have been associated with compulsive behaviors and/or loss of impulse control, which has manifested as pathological gambling, libido increases (hypersexuality), and/or binge eating. Causality has not been established, and controversy exists as to whether this phenomenon is related to the underlying disease, prior behaviors/addictions and/or drug therapy. Dose reduction or discontinuation of therapy has been reported to reverse these behaviors in some, but not all cases. Melanoma: Risk for melanoma development is increased in Parkinson's disease patients; drug causation or factors contributing to risk have not been established. Patients should be monitored closely and periodic skin examinations should be performed. Neuroleptic malignant syndrome: Has been associated with neuroleptic malignant syndrome (associated with dose reduction or abrupt discontinuation). Suicidal ideation: There have been reports of suicidal ideation/attempt in patients with and without a history of psychiatric illness. May exacerbate mental problems in patients with a history of mental illness.
Disease-related concerns: Cardiovascular disease: Use with caution in patients with heart failure, peripheral edema, or orthostatic hypotension; dosage reduction may be required. Eczema: Use with caution in patients with a history of recurrent and eczematoid dermatitis. Glaucoma: Avoid in untreated angle closure glaucoma. Hepatic impairment: Use with caution in patients with hepatic impairment; rarely, elevations in transaminases have been reported. Influenza A: Appropriate use: Consult current guidelines. Due to increased resistance, the ACIP has recommended that rimantadine and amantadine no longer be used for the treatment or prophylaxis of influenza A in the United States until susceptibility has been re-established. Parkinson's disease: Appropriate use: When treating Parkinson's disease, do not discontinue abruptly. In many patients, the therapeutic benefits of amantadine are limited to a few months. Psychosis: Use with caution in patients with uncontrolled psychosis or severe psychoneurosis. Renal impairment: Use with caution in patients with renal impairment; dosage reduction recommended. Seizure disorder: Use with caution in patients with a history of seizure disorder.
Concurrent drug therapy issues: CNS stimulants: Use with caution in patients receiving CNS stimulant drugs.
Special populations: Elderly: Use with caution in the elderly; may be more susceptible to CNS effects (using 2 divided daily doses may minimize this effect). These patients may require dosage reductions based on renal function. Pediatrics: Safety and efficacy have not been established in children <1 year of age.
Other warnings/precautions: Withdrawal syndrome: May cause agitation, anxiety, delirium, delusions, depression, hallucinations, paranoia, parkinsonian crisis, slurred speech, or stupor. Upon discontinuation of amantadine therapy, gradually taper dose.
DRUG INTERACTIONS
Antipsychotics (Atypical): May diminish the therapeutic effect of Anti-Parkinson's Agents (Dopamine Agonist). Risk D: Consider therapy modification
Antipsychotics (Typical): May diminish the therapeutic effect of Anti-Parkinson's Agents (Dopamine Agonist). Risk D: Consider therapy modification
Influenza Virus Vaccine: Antiviral Agents (Influenza A and B) may diminish the therapeutic effect of Influenza Virus Vaccine. This only pertains to live, attentuated influenza virus vaccine. Risk D: Consider therapy modification
MAO Inhibitors: May enhance the orthostatic effect of Orthostasis Producing Agents. Risk C: Monitor therapy
Metoclopramide: May diminish the therapeutic effect of Anti-Parkinson's Agents (Dopamine Agonist). Risk C: Monitor therapy
Trimethoprim: May enhance the adverse/toxic effect of Amantadine. Specifically, the risk of myoclonus and/or delirium may be increased. Amantadine may increase the serum concentration of Trimethoprim. Trimethoprim may increase the serum concentration of Amantadine. Risk C: Monitor therapy
ETHANOL / NUTRITION / HERB INTERACTIONS — Ethanol: Avoid ethanol (may increase CNS adverse effects).
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — Teratogenic effects were observed in animal studies; limited data in humans. Impaired fertility has also been reported during animal studies and during human in vitro fertilization.
LACTATION — Enters breast milk/not recommended
PRICING — (data from drugstore.com)
Capsules (Amantadine HCl)
100 mg (30): $21.99
Syrup (Amantadine HCl)
50 mg/5 mL (120): $15.98
Tablets (Amantadine HCl)
100 mg (30): $33.99
MONITORING PARAMETERS — Renal function, Parkinson's symptoms, mental status, influenza symptoms, blood pressure
CANADIAN BRAND NAMES — Endantadine®; PMS-Amantadine; Symmetrel®
INTERNATIONAL BRAND NAMES — a.m.t. (DE); Amanda (TW); Amandin (TW); Amandine (UY); Amanta (KP); Amantadin (EE); Amantadin-ratiopharm (PL); Amantadina Juventus (ES); Amantadina Llorente (ES); Amantan (BE, LU); Amantix (CO, PL); Amantrel (IN); Amazolon (JP); Atarin (CL, FI); Boidan (JP); Enzil (TW); Hofcomant (AT, FI); Influ (TW); Influ-A (IL); Mantadan (IT); Mantadix (FR, LU); Mantidan (BR); Paritrel (IL); PK-Merz (AE, AT, BF, BG, BH, BJ, CH, CI, CN, CR, CY, CZ, DE, DO, EE, EG, ET, GH, GM, GN, GT, HK, HN, HU, IL, IQ, IR, JO, KE, KP, KW, LB, LR, LU, LY, MA, ML, MR, MU, MW, MX, MY, NE, NG, NI, OM, PA, PK, PT, PY, QA, SA, SC, SD, SL, SN, SV, SY, TN, TW, TZ, UG, YE, ZA, ZM, ZW); Prayanol (CN); Symmetrel (AE, AT, AU, BH, CH, CY, EG, GB, GR, HR, IE, IL, IQ, IR, JO, KW, LB, LY, NL, NO, OM, QA, SA, SY, VE, YE); Viregyt-K (BG, HU, PL); Virofral (DK); Virosol (AR)
MECHANISM OF ACTION — As an antiviral, blocks the uncoating of influenza A virus preventing penetration of virus into host; antiparkinsonian activity may be due to its blocking the reuptake of dopamine into presynaptic neurons or by increasing dopamine release from presynaptic fibers
PHARMACODYNAMICS / KINETICS
Onset of action: Antidyskinetic: Within 48 hours
Absorption: Well absorbed
Distribution: Vd: Normal: 1.5-6.1 L/kg; Renal failure: 5.1 +/- 0.2 L/kg; in saliva, tear film, and nasal secretions; in animals, tissue (especially lung) concentrations higher than serum concentrations; crosses blood-brain barrier
Protein binding: Normal renal function: ~67%; Hemodialysis: ~59%
Metabolism: Not appreciable; small amounts of an acetyl metabolite identified
Bioavailability: 86% to 90%
Half-life elimination: Normal renal function: 16 +/- 6 hours (9-31 hours); Healthy, older (≥ 60 years) males: 29 hours (range: 20-41 hours); End-stage renal disease: 7-10 days
Time to peak, plasma: 2-4 hours
Excretion: Urine (80% to 90% unchanged) by glomerular filtration and tubular secretion
PATIENT INFORMATION — Do not abruptly discontinue therapy; it may precipitate a parkinsonian crisis. May impair ability to perform activities requiring mental alertness or coordination. Take throughout flu season or for at least 10 days following vaccination for effective prophylaxis. Take second dose of the day in early afternoon to decrease incidence of insomnia.
Sound-alike/look-alike issues:
Amantadine may be confused with ranitidine, rimantadine
Symmetrel® may be confused with Synthroid®
International issues:
Symmetrel® may be confused with Somatrel® which is a brand name for somatorelin in Denmark
SPECIAL ALERTS
CDC Updated Interim Recommendations for the Use of Antivirals During 2009-2010 Influenza Season - September 2009
The Centers for Disease Control and Prevention (CDC) has issued interim recommendations for the use of antivirals for the treatment and prevention of influenza during the 2009-2010 season. These recommendations apply to seasonal influenza and the 2009 H1N1 influenza (formerly known as novel influenza A [H1N1]). Antiviral doses and schedules for treatment or chemoprophylaxis of 2009 H1N1 influenza are the same as those recommended for seasonal influenza. Additionally, the U.S. Food and Drug Administration (FDA) has issued a temporary Emergency Use Authorization to allow the use of oseltamivir in children <1 year of age. The following is a summary of the updated interim recommendations:
(1) Treatment with oseltamivir or zanamivir is recommended in any patient hospitalized with suspected or confirmed influenza.
(2) Treatment with oseltamivir or zanamivir is generally recommended for patients who are at higher risk for influenza-related complications (eg, children <5 years of age, adults ≥ 65 years of age, pregnant women, immunosuppressed patients, patients <19 years of age receiving long-term aspirin therapy, and persons with chronic health conditions such as pulmonary, cardiovascular, renal, hepatic, hematologic, neurologic, neuromuscular, or metabolic disorders).
(3) Any suspected influenza patient with warning signs/symptoms (eg, dyspnea, tachypnea, unexplained oxygen desaturation) consistent with an acute lower respiratory tract illness should promptly receive empiric antiviral therapy.
(4) Treatment, when indicated, should be started without delay (within 48 hours of illness onset) and should not await laboratory confirmation. Early initiation is more likely to provide benefit.
(5) Treatment or prophylaxis is generally not required in patients with suspected influenza who present with uncomplicated febrile illness or are not at higher risk for complications.
(6) Postexposure antiviral chemoprophylaxis with oseltamivir or zanamivir may be considered in the following populations after an exposure or close contact of a person with suspected, probable, or confirmed influenza during that person's infectious period ("infectious period" is defined as 1 day before through 24 hours after fever ends):
- Persons at higher risk of influenza complications
- Healthcare and public health workers or first responders
(7) Chemoprophylaxis is generally not recommended if more than 48 hours has lapsed since last exposure to the infectious person, and is not indicated if the exposure did not occur during the infectious period. Chemoprophylaxis is not recommended in healthy children or adults after a potential exposure in the community, school, camp, or other setting.
(8) Currently circulating 2009 H1N1 viruses are susceptible to oseltamivir and zanamivir, but resistant to amantadine and rimantadine. Oseltamivir-resistant 2009 H1N1 viruses have been identified, most commonly observed during chemoprophylaxis or in immunocompromised patients receiving treatment for influenza. Conversely, regular seasonal influenza A (H1N1) is commonly resistant to oseltamivir, but is typically susceptible to rimantadine and amantadine. However, at present, oseltamivir or zanamivir is appropriate for the treatment of seasonal H1N1 influenza. If oseltamivir-resistant seasonal H1N1 viruses become more common or are identified in community outbreaks, zanamivir (or a combination of oseltamivir and rimantadine or amantadine) should be considered for empiric treatment of suspected oseltamivir-resistant seasonal human influenza A (H1N1) virus infection.
CDC recommendations are changing frequently as more information on antiviral susceptibilities and effectiveness becomes available. For the most recent recommendations and information from the CDC, please refer to:
http://www.cdc.gov/h1n1flu/recommendations.htm
http://www.cdc.gov/h1n1flu/guidance/
U.S. BRAND NAMES — Symmetrel®
PHARMACOLOGIC CATEGORY
Anti-Parkinson's Agent, Dopamine Agonist
Antiviral Agent
Antiviral Agent, Adamantane
DOSING: ADULTS
Influenza A treatment/prophylaxis:Note: Due to issues of resistance, amantadine is no longer recommended for the treatment or prophylaxis of influenza A. Please refer to the current ACIP recommendations. The following is based on the manufacturer's labeling:
Influenza A treatment: Oral: 200 mg once daily or 100 mg twice daily (may be preferred to reduce CNS effects); Note: Initiate within 24-48 hours after onset of symptoms; continue for 24-48 hours after symptom resolution (duration of therapy is generally 3-5 days).
Influenza A prophylaxis: Oral: 200 mg once daily or 100 mg twice daily (may be preferred to reduce CNS effects). Note: Continue prophylaxis throughout the peak influenza activity in the community or throughout the entire influenza season in patients who cannot be vaccinated. Development of immunity following vaccination takes ~2 weeks; amantadine therapy should be considered for high-risk patients from the time of vaccination until immunity has developed.
Drug-induced extrapyramidal symptoms: Oral: 100 mg twice daily; may increase to 300 mg/day in divided doses, if needed
Parkinson's disease: Oral: Usual dose: 100 mg twice daily as monotherapy; may increase to 400 mg/day in divided doses, if needed, with close monitoring. Note: Patients with a serious concomitant illness or those receiving high doses of other anti-parkinson drugs should be started at 100 mg/day; may increase to 100 mg twice daily, if needed, after one to several weeks.
DOSING: PEDIATRIC
(For additional information see "Amantadine: Pediatric drug information")
Influenza A treatment/prophylaxis: Oral: Note: Due to issues of resistance, amantadine is no longer recommended for the treatment or prophylaxis of influenza A. Please refer to the current ACIP recommendations. The following is based on the manufacturer's labeling and past ACIP dosing recommendations:
Influenza A treatment:
1-9 years: 5 mg/kg/day in 2 divided doses (manufacturers range: 4.4-8.8 mg/kg/day); maximum dose: 150 mg/day
≥ 10 years and <40 kg: 5 mg/kg/day in 2 divided doses; maximum dose: 150 mg/day (CDC, 2003)
≥ 10 years and ≥ 40 kg: 100 mg twice daily (CDC, 2003)
Note: Initiate within 24-48 hours after onset of symptoms; continue for 24-48 hours after symptom resolution (duration of therapy is generally 3-5 days)
Influenza A prophylaxis: Refer to "Influenza A treatment" dosing. Note: Continue prophylaxis throughout the peak influenza activity in the community or throughout the entire influenza season in patients who cannot be vaccinated. Development of immunity following vaccination takes ~2 weeks; amantadine therapy should be considered for high-risk patients from the time of vaccination until immunity has developed. For children <9 years receiving influenza vaccine for the first time, amantadine prophylaxis should continue for 6 weeks (4 weeks after the first dose and 2 weeks after the second dose).
DOSING: ELDERLY — Patients ≥ 65 years: Adjust dose based on renal function; some patients tolerate the drug better when it is given in 2 divided daily doses (to avoid adverse neurologic reactions).
Influenza A treatment/prophylaxis: 100 mg once daily
DOSING: RENAL IMPAIRMENT
Clcr 30-50 mL/minute: Administer 200 mg on day 1, then 100 mg/day
Clcr 15-29 mL/minute: Administer 200 mg on day 1, then 100 mg on alternate days
Clcr <15 mL/minute: Administer 200 mg every 7 days
Hemodialysis: Administer 200 mg every 7 days
Peritoneal dialysis: No supplemental dose is needed
Continuous arteriovenous or venous-venous hemofiltration: No supplemental dose is needed
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, as hydrochloride: 100 mg
Capsule, softgel, as hydrochloride: 100 mg
Solution, oral, as hydrochloride: 50 mg/5 mL (473 mL)
Syrup, oral, as hydrochloride: 50 mg/5 mL (10 mL, 480 mL)
Tablet, as hydrochloride: 100 mg
Symmetrel®: 100 mg
DOSAGE FORMS: CONCISE
Capsule: 100 mg
Capsule, softgel: 100 mg
Solution, oral: 50 mg/5 mL
Syrup, oral: 50 mg/5 mL
Tablet: 100 mg
Symmetrel®: 100 mg
GENERIC EQUIVALENT AVAILABLE — Yes
USE — Prophylaxis and treatment of influenza A viral infection (per manufacturer labeling; also refer to current ACIP guidelines for recommendations during current flu season); treatment of parkinsonism; treatment of drug-induced extrapyramidal symptoms
Note: In certain circumstances, the ACIP recommends use of amantadine in combination with oseltamivir for the treatment or prophylaxis of influenza A infection when resistance to oseltamivir is suspected.
ADVERSE REACTIONS SIGNIFICANT
1% to 10%:
Cardiovascular: Orthostatic hypotension, peripheral edema
Central nervous system: Agitation, anxiety, ataxia, confusion, delirium, depression, dizziness, dream abnormality, fatigue, hallucinations, headache, insomnia, irritability, lightheadedness, nervousness, somnolence
Dermatologic: Livedo reticularis
Gastrointestinal: Anorexia, constipation, diarrhea, nausea, xerostomia
Respiratory: Dry nose
<1% (Limited to important or life-threatening): Aggressive behavior, agranulocytosis, alkaline phosphatase increased, allergic reaction, ALT increased, AST increased, amnesia, anaphylaxis, arrhythmia, bilirubin increased, BUN increased, cardiac arrest, coma, CPK increased, creatinine increased, delusions, diaphoresis, dysphagia, dyspnea, eczematoid dermatitis, euphoria, GGT increased, heart failure, hyperkinesis, LDH increased, leukopenia, mania, neutropenia, neuroleptic malignant syndrome (NMS; associated with dosage reduction or abrupt withdrawal of amantadine), oculogyric episodes, paresthesia, photosensitivity, psychosis, pulmonary edema, rash, respiratory failure (acute), seizures, suicidal ideation, suicide, urinary retention, withdrawal reactions (may include delirium, hallucinations, and psychosis), visual disturbances
Reported with dopamine agonists: Impulsive/compulsive behaviors (eg, pathological gambling, hypersexuality, binge eating)
CONTRAINDICATIONS — Hypersensitivity to amantadine or any component of the formulation
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving). Impulse control disorders: Dopamine agonists used for Parkinson's disease or restless legs syndrome have been associated with compulsive behaviors and/or loss of impulse control, which has manifested as pathological gambling, libido increases (hypersexuality), and/or binge eating. Causality has not been established, and controversy exists as to whether this phenomenon is related to the underlying disease, prior behaviors/addictions and/or drug therapy. Dose reduction or discontinuation of therapy has been reported to reverse these behaviors in some, but not all cases. Melanoma: Risk for melanoma development is increased in Parkinson's disease patients; drug causation or factors contributing to risk have not been established. Patients should be monitored closely and periodic skin examinations should be performed. Neuroleptic malignant syndrome: Has been associated with neuroleptic malignant syndrome (associated with dose reduction or abrupt discontinuation). Suicidal ideation: There have been reports of suicidal ideation/attempt in patients with and without a history of psychiatric illness. May exacerbate mental problems in patients with a history of mental illness.
Disease-related concerns: Cardiovascular disease: Use with caution in patients with heart failure, peripheral edema, or orthostatic hypotension; dosage reduction may be required. Eczema: Use with caution in patients with a history of recurrent and eczematoid dermatitis. Glaucoma: Avoid in untreated angle closure glaucoma. Hepatic impairment: Use with caution in patients with hepatic impairment; rarely, elevations in transaminases have been reported. Influenza A: Appropriate use: Consult current guidelines. Due to increased resistance, the ACIP has recommended that rimantadine and amantadine no longer be used for the treatment or prophylaxis of influenza A in the United States until susceptibility has been re-established. Parkinson's disease: Appropriate use: When treating Parkinson's disease, do not discontinue abruptly. In many patients, the therapeutic benefits of amantadine are limited to a few months. Psychosis: Use with caution in patients with uncontrolled psychosis or severe psychoneurosis. Renal impairment: Use with caution in patients with renal impairment; dosage reduction recommended. Seizure disorder: Use with caution in patients with a history of seizure disorder.
Concurrent drug therapy issues: CNS stimulants: Use with caution in patients receiving CNS stimulant drugs.
Special populations: Elderly: Use with caution in the elderly; may be more susceptible to CNS effects (using 2 divided daily doses may minimize this effect). These patients may require dosage reductions based on renal function. Pediatrics: Safety and efficacy have not been established in children <1 year of age.
Other warnings/precautions: Withdrawal syndrome: May cause agitation, anxiety, delirium, delusions, depression, hallucinations, paranoia, parkinsonian crisis, slurred speech, or stupor. Upon discontinuation of amantadine therapy, gradually taper dose.
DRUG INTERACTIONS
Antipsychotics (Atypical): May diminish the therapeutic effect of Anti-Parkinson's Agents (Dopamine Agonist). Risk D: Consider therapy modification
Antipsychotics (Typical): May diminish the therapeutic effect of Anti-Parkinson's Agents (Dopamine Agonist). Risk D: Consider therapy modification
Influenza Virus Vaccine: Antiviral Agents (Influenza A and B) may diminish the therapeutic effect of Influenza Virus Vaccine. This only pertains to live, attentuated influenza virus vaccine. Risk D: Consider therapy modification
MAO Inhibitors: May enhance the orthostatic effect of Orthostasis Producing Agents. Risk C: Monitor therapy
Metoclopramide: May diminish the therapeutic effect of Anti-Parkinson's Agents (Dopamine Agonist). Risk C: Monitor therapy
Trimethoprim: May enhance the adverse/toxic effect of Amantadine. Specifically, the risk of myoclonus and/or delirium may be increased. Amantadine may increase the serum concentration of Trimethoprim. Trimethoprim may increase the serum concentration of Amantadine. Risk C: Monitor therapy
ETHANOL / NUTRITION / HERB INTERACTIONS — Ethanol: Avoid ethanol (may increase CNS adverse effects).
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — Teratogenic effects were observed in animal studies; limited data in humans. Impaired fertility has also been reported during animal studies and during human in vitro fertilization.
LACTATION — Enters breast milk/not recommended
PRICING — (data from drugstore.com)
Capsules (Amantadine HCl)
100 mg (30): $21.99
Syrup (Amantadine HCl)
50 mg/5 mL (120): $15.98
Tablets (Amantadine HCl)
100 mg (30): $33.99
MONITORING PARAMETERS — Renal function, Parkinson's symptoms, mental status, influenza symptoms, blood pressure
CANADIAN BRAND NAMES — Endantadine®; PMS-Amantadine; Symmetrel®
INTERNATIONAL BRAND NAMES — a.m.t. (DE); Amanda (TW); Amandin (TW); Amandine (UY); Amanta (KP); Amantadin (EE); Amantadin-ratiopharm (PL); Amantadina Juventus (ES); Amantadina Llorente (ES); Amantan (BE, LU); Amantix (CO, PL); Amantrel (IN); Amazolon (JP); Atarin (CL, FI); Boidan (JP); Enzil (TW); Hofcomant (AT, FI); Influ (TW); Influ-A (IL); Mantadan (IT); Mantadix (FR, LU); Mantidan (BR); Paritrel (IL); PK-Merz (AE, AT, BF, BG, BH, BJ, CH, CI, CN, CR, CY, CZ, DE, DO, EE, EG, ET, GH, GM, GN, GT, HK, HN, HU, IL, IQ, IR, JO, KE, KP, KW, LB, LR, LU, LY, MA, ML, MR, MU, MW, MX, MY, NE, NG, NI, OM, PA, PK, PT, PY, QA, SA, SC, SD, SL, SN, SV, SY, TN, TW, TZ, UG, YE, ZA, ZM, ZW); Prayanol (CN); Symmetrel (AE, AT, AU, BH, CH, CY, EG, GB, GR, HR, IE, IL, IQ, IR, JO, KW, LB, LY, NL, NO, OM, QA, SA, SY, VE, YE); Viregyt-K (BG, HU, PL); Virofral (DK); Virosol (AR)
MECHANISM OF ACTION — As an antiviral, blocks the uncoating of influenza A virus preventing penetration of virus into host; antiparkinsonian activity may be due to its blocking the reuptake of dopamine into presynaptic neurons or by increasing dopamine release from presynaptic fibers
PHARMACODYNAMICS / KINETICS
Onset of action: Antidyskinetic: Within 48 hours
Absorption: Well absorbed
Distribution: Vd: Normal: 1.5-6.1 L/kg; Renal failure: 5.1 +/- 0.2 L/kg; in saliva, tear film, and nasal secretions; in animals, tissue (especially lung) concentrations higher than serum concentrations; crosses blood-brain barrier
Protein binding: Normal renal function: ~67%; Hemodialysis: ~59%
Metabolism: Not appreciable; small amounts of an acetyl metabolite identified
Bioavailability: 86% to 90%
Half-life elimination: Normal renal function: 16 +/- 6 hours (9-31 hours); Healthy, older (≥ 60 years) males: 29 hours (range: 20-41 hours); End-stage renal disease: 7-10 days
Time to peak, plasma: 2-4 hours
Excretion: Urine (80% to 90% unchanged) by glomerular filtration and tubular secretion
PATIENT INFORMATION — Do not abruptly discontinue therapy; it may precipitate a parkinsonian crisis. May impair ability to perform activities requiring mental alertness or coordination. Take throughout flu season or for at least 10 days following vaccination for effective prophylaxis. Take second dose of the day in early afternoon to decrease incidence of insomnia.
Alvimopan
MEDICATION SAFETY ISSUES
Sound-alike/look-alike issues:
Alvimopan may be confused with almotriptan
U.S. BRAND NAMES — Entereg®
PHARMACOLOGIC CATEGORY
Gastrointestinal Agent, Miscellaneous
Opioid Antagonist, Peripherally-Acting
DOSING: ADULTS — Note: For hospital use only.
Management of postoperative ileus: Oral:
Initial: 12 mg administered 30 minutes to 5 hours prior to surgery
Maintenance: 12 mg twice daily beginning the day after surgery for a maximum of 7 days or until discharged from hospital (maximum total treatment doses: 15 doses)
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT
Mild-to-severe impairment: No adjustment needed; use caution.
ESRD: Use not recommended.
DOSING: HEPATIC IMPAIRMENT
Mild-to-moderate impairment (Child-Pugh class A and B): No adjustment needed; use caution.
Severe impairment (Child-Pugh class C): Use not recommended.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics ); consult specific product labeling.
Capsule:
Entereg®: 12 mg
DOSAGE FORMS: CONCISE
Capsule:
Entereg®: 12 mg
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Patient must be hospitalized. Initial dose should be administered 30 minutes to 5 hours prior to surgery.
USE — Accelerate the time to upper and lower GI recovery following partial large or small bowel resection surgery with primary anastomosis
ADVERSE REACTIONS SIGNIFICANT — Note: Incidence reported limited to bowel resection patients only. 1% to 10%:
Endocrine & metabolic: Hypokalemia (10%)
Gastrointestinal: Dyspepsia (7%)
Genitourinary: Urinary retention (3%)
Hematologic: Anemia (5%)
Neuromuscular & skeletal: Back pain (3%)
CONTRAINDICATIONS — Patients who have taken therapeutic doses of opioids for more than 7 consecutive days immediately prior to alvimopan
WARNINGS / PRECAUTIONS
Boxed warnings: Appropriate use: See "Other warnings/precautions" below.
Concerns related to adverse effects: Cardiovascular effects: A trend towards an increased incidence of MI was observed in alvimopan (low dose) treated patients compared to placebo in a 12-month study in patients treated with opioids for chronic pain. MI was generally observed more frequently in the initial 1-4 months of treatment. Other studies have not observed this trend and a causal relationship has not been found.
Disease-related concerns: Complete bowel obstruction: Use not recommended in patients undergoing surgery for complete bowel obstruction. Hepatic impairment: Use with caution in patients with mild-to-moderate hepatic impairment (Child-Pugh classes A and B); use not recommended with severe impairment (Child-Pugh class C). Renal impairment: Use with caution in patients with renal impairment; use not recommended in patients with ESRD.
Concurrent drug therapy issues: Opioids: Use with caution in patients recently exposed to opioids; may be more sensitive to gastrointestinal adverse effects (eg, abdominal pain, diarrhea, nausea and vomiting). Contraindicated in patients who have received therapeutic opioids for >7 consecutive days immediately prior to use.
Special populations: Pediatrics: Safety and efficacy have not been established in children.
Other warnings/precautions: Appropriate use: [U.S. Boxed Warning]: For short-term (≤ 15 doses) hospital use only. Only hospitals that have registered through the ENTEREG Access Support and Education (E.A.S.E.™ ) Program and met all requirements may use. It will not be dispensed to patients who have been discharged from the hospital.
RESTRICTIONS — Only hospitals enrolled in the ENTEREG Access Support and Education (E.A.S.E.™ ) Program may administer this medication. Hospital staff must be educated on need to limit to short-term (no more than 15 doses) and inpatient use. Hospitals may contact the E.A.S.E.™ program at 1-866-423-6567 (1-866-4ADOLOR).
METABOLISM / TRANSPORT EFFECTS — Substrate of P-glycoprotein
DRUG INTERACTIONS
Analgesics (Opioid): May enhance the adverse/toxic effect of Alvimopan. This is most notable for patients receiving long-term (i.e., more than 7 days) opiates prior to alvimopan initiation. Management: Alvimopan is contraindicated in patients receiving therapeutic doses of opioids for more than 7 consecutive days immediately prior to alvimopan initiation. Risk D: Consider therapy modification
ETHANOL / NUTRITION / HERB INTERACTIONS — Food: When administered with a high-fat meal, extent and rate of absorption may be reduced (Cmax and AUC decreased by ~38% and 21%, respectively).
PREGNANCY RISK FACTOR — B (show table)
PREGNANCY IMPLICATIONS — Animal studies have not shown teratogenic effects to the fetus. However, there are no adequate and well-controlled studies in pregnant women; use during pregnancy only if clearly needed.
LACTATION — Excretion in breast milk unknown/use caution
DIETARY CONSIDERATIONS — Take with or without food; high-fat meals may decrease the rate and extent of absorption
MECHANISM OF ACTION — An opioid receptor antagonist which blocks opioid binding at the mu receptor; alvimopan has restricted ability to cross the blood-brain barrier at therapeutic doses. It selectively and competitively binds to the GI tract mu opioid receptors and antagonizes the peripheral effects of opioids on gastrointestinal motility and secretion. Does not affect opioid analgesic effects or induce opioid withdrawal symptoms.
PHARMACODYNAMICS / KINETICS
Distribution: Vd: 20-40 L
Protein binding: Parent drug: 80%; metabolite: 94% (both primarily to albumin)
Metabolism: Hydrolyzed to an amide hydrolysis compound (active metabolite) by gut microflora; further metabolism of active metabolite to glucuronide conjugates and other minor metabolites.
Bioavailability: ~6% (range: 1% to 19%)
Half-life elimination: 10-18 hours
Time to peak, plasma: ~2 hours
Excretion: Urine (35% as unchanged drug and metabolites); feces (via biliary excretion)
Sound-alike/look-alike issues:
Alvimopan may be confused with almotriptan
U.S. BRAND NAMES — Entereg®
PHARMACOLOGIC CATEGORY
Gastrointestinal Agent, Miscellaneous
Opioid Antagonist, Peripherally-Acting
DOSING: ADULTS — Note: For hospital use only.
Management of postoperative ileus: Oral:
Initial: 12 mg administered 30 minutes to 5 hours prior to surgery
Maintenance: 12 mg twice daily beginning the day after surgery for a maximum of 7 days or until discharged from hospital (maximum total treatment doses: 15 doses)
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT
Mild-to-severe impairment: No adjustment needed; use caution.
ESRD: Use not recommended.
DOSING: HEPATIC IMPAIRMENT
Mild-to-moderate impairment (Child-Pugh class A and B): No adjustment needed; use caution.
Severe impairment (Child-Pugh class C): Use not recommended.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics ); consult specific product labeling.
Capsule:
Entereg®: 12 mg
DOSAGE FORMS: CONCISE
Capsule:
Entereg®: 12 mg
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Patient must be hospitalized. Initial dose should be administered 30 minutes to 5 hours prior to surgery.
USE — Accelerate the time to upper and lower GI recovery following partial large or small bowel resection surgery with primary anastomosis
ADVERSE REACTIONS SIGNIFICANT — Note: Incidence reported limited to bowel resection patients only. 1% to 10%:
Endocrine & metabolic: Hypokalemia (10%)
Gastrointestinal: Dyspepsia (7%)
Genitourinary: Urinary retention (3%)
Hematologic: Anemia (5%)
Neuromuscular & skeletal: Back pain (3%)
CONTRAINDICATIONS — Patients who have taken therapeutic doses of opioids for more than 7 consecutive days immediately prior to alvimopan
WARNINGS / PRECAUTIONS
Boxed warnings: Appropriate use: See "Other warnings/precautions" below.
Concerns related to adverse effects: Cardiovascular effects: A trend towards an increased incidence of MI was observed in alvimopan (low dose) treated patients compared to placebo in a 12-month study in patients treated with opioids for chronic pain. MI was generally observed more frequently in the initial 1-4 months of treatment. Other studies have not observed this trend and a causal relationship has not been found.
Disease-related concerns: Complete bowel obstruction: Use not recommended in patients undergoing surgery for complete bowel obstruction. Hepatic impairment: Use with caution in patients with mild-to-moderate hepatic impairment (Child-Pugh classes A and B); use not recommended with severe impairment (Child-Pugh class C). Renal impairment: Use with caution in patients with renal impairment; use not recommended in patients with ESRD.
Concurrent drug therapy issues: Opioids: Use with caution in patients recently exposed to opioids; may be more sensitive to gastrointestinal adverse effects (eg, abdominal pain, diarrhea, nausea and vomiting). Contraindicated in patients who have received therapeutic opioids for >7 consecutive days immediately prior to use.
Special populations: Pediatrics: Safety and efficacy have not been established in children.
Other warnings/precautions: Appropriate use: [U.S. Boxed Warning]: For short-term (≤ 15 doses) hospital use only. Only hospitals that have registered through the ENTEREG Access Support and Education (E.A.S.E.™ ) Program and met all requirements may use. It will not be dispensed to patients who have been discharged from the hospital.
RESTRICTIONS — Only hospitals enrolled in the ENTEREG Access Support and Education (E.A.S.E.™ ) Program may administer this medication. Hospital staff must be educated on need to limit to short-term (no more than 15 doses) and inpatient use. Hospitals may contact the E.A.S.E.™ program at 1-866-423-6567 (1-866-4ADOLOR).
METABOLISM / TRANSPORT EFFECTS — Substrate of P-glycoprotein
DRUG INTERACTIONS
Analgesics (Opioid): May enhance the adverse/toxic effect of Alvimopan. This is most notable for patients receiving long-term (i.e., more than 7 days) opiates prior to alvimopan initiation. Management: Alvimopan is contraindicated in patients receiving therapeutic doses of opioids for more than 7 consecutive days immediately prior to alvimopan initiation. Risk D: Consider therapy modification
ETHANOL / NUTRITION / HERB INTERACTIONS — Food: When administered with a high-fat meal, extent and rate of absorption may be reduced (Cmax and AUC decreased by ~38% and 21%, respectively).
PREGNANCY RISK FACTOR — B (show table)
PREGNANCY IMPLICATIONS — Animal studies have not shown teratogenic effects to the fetus. However, there are no adequate and well-controlled studies in pregnant women; use during pregnancy only if clearly needed.
LACTATION — Excretion in breast milk unknown/use caution
DIETARY CONSIDERATIONS — Take with or without food; high-fat meals may decrease the rate and extent of absorption
MECHANISM OF ACTION — An opioid receptor antagonist which blocks opioid binding at the mu receptor; alvimopan has restricted ability to cross the blood-brain barrier at therapeutic doses. It selectively and competitively binds to the GI tract mu opioid receptors and antagonizes the peripheral effects of opioids on gastrointestinal motility and secretion. Does not affect opioid analgesic effects or induce opioid withdrawal symptoms.
PHARMACODYNAMICS / KINETICS
Distribution: Vd: 20-40 L
Protein binding: Parent drug: 80%; metabolite: 94% (both primarily to albumin)
Metabolism: Hydrolyzed to an amide hydrolysis compound (active metabolite) by gut microflora; further metabolism of active metabolite to glucuronide conjugates and other minor metabolites.
Bioavailability: ~6% (range: 1% to 19%)
Half-life elimination: 10-18 hours
Time to peak, plasma: ~2 hours
Excretion: Urine (35% as unchanged drug and metabolites); feces (via biliary excretion)
Aluminum sulfate calcium acetate
U.S. BRAND NAMES — Domeboro® [OTC]; Gordon Boro-Packs [OTC]; Pedi-Boro® [OTC]
PHARMACOLOGIC CATEGORY
Topical Skin Product
DOSING: ADULTS — Dermal inflammation, dermatitis: Topical: Soak affected area in the solution 2-4 times/day for 15-30 minutes or apply wet dressing soaked in the solution for more extended periods; rewet dressing with solution 2-4 times/day every 15-30 minutes
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Powder, for topical solution:
Domeboro®: Aluminum sulfate 1191 mg and calcium acetate 839 mg per packet (12s, 100s)
Gordon Boro-Packs: Aluminum sulfate 49% and calcium acetate 51% per packet (100s)
Pedi-Boro®: Aluminum sulfate 1191 mg and calcium acetate 839 mg per packet (12s, 100s)
DOSAGE FORMS: CONCISE
Powder, for topical solution:
Domeboro® [OTC]: Aluminum sulfate 1191 mg and calcium acetate 839 mg per packet (12s, 100s)
Gordon Boro-Packs: Aluminum sulfate 49% and calcium acetate 51% per packet (100s)
Pedi-Boro® [OTC]: Aluminum sulfate 1191 mg and calcium acetate 839 mg per packet (12s, 100s)
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — For external use only. Do not occlude dressing to prevent evaporation.
USE — Astringent wet dressing for relief of inflammatory conditions of the skin; reduce weeping that may occur in dermatitis
WARNINGS / PRECAUTIONS
Other warnings/precautions: Appropriate use: For external use only; avoid contact with eyes. Discontinue use if irritation occurs. OTC duration of therapy: Not for OTC use >7 days.
DRUG INTERACTIONS
Bisphosphonate Derivatives: Calcium Salts may decrease the absorption of Bisphosphonate Derivatives. Exceptions: Pamidronate; Zoledronic Acid. Risk D: Consider therapy modification
Calcium Channel Blockers: Calcium Salts may diminish the therapeutic effect of Calcium Channel Blockers. Risk C: Monitor therapy
CefTRIAXone: Calcium Salts (Intravenous) may enhance the adverse/toxic effect of CefTRIAXone. Ceftriaxone binds to calcium forming an insoluble precipitate. Management: Use of ceftriaxone with calcium-containing solutions within 48 hours of one another is contraindicated in neonates (28 days of age or younger). In older patients, flush lines with compatible fluid between administration. Risk D: Consider therapy modification
DOBUTamine: Calcium Salts may diminish the therapeutic effect of DOBUTamine. Risk C: Monitor therapy
Eltrombopag: Calcium Salts may decrease the serum concentration of Eltrombopag. Management: Separate administration of eltrombopag and any polyvalent cation (e.g., calcium-containing products) by at least 4 hours. Risk D: Consider therapy modification
Estramustine: Calcium Salts may decrease the absorption of Estramustine. Risk D: Consider therapy modification
Phosphate Supplements: Calcium Salts may decrease the absorption of Phosphate Supplements. Risk D: Consider therapy modification
Quinolone Antibiotics: Calcium Salts may decrease the absorption of Quinolone Antibiotics. Of concern only with oral administration of both agents. Exceptions: Moxifloxacin. Risk D: Consider therapy modification
Thiazide Diuretics: May decrease the excretion of Calcium Salts. Continued concomitant use can also result in metabolic alkalosis. Risk C: Monitor therapy
Thyroid Products: Calcium Salts may diminish the therapeutic effect of Thyroid Products. Management: Separate the doses of the thyroid product and the oral calcium supplement by at least 4 hours. Risk D: Consider therapy modification
Trientine: Calcium Salts may decrease the serum concentration of Trientine. Trientine may decrease the serum concentration of Calcium Salts. Risk D: Consider therapy modification
PHARMACOLOGIC CATEGORY
Topical Skin Product
DOSING: ADULTS — Dermal inflammation, dermatitis: Topical: Soak affected area in the solution 2-4 times/day for 15-30 minutes or apply wet dressing soaked in the solution for more extended periods; rewet dressing with solution 2-4 times/day every 15-30 minutes
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Powder, for topical solution:
Domeboro®: Aluminum sulfate 1191 mg and calcium acetate 839 mg per packet (12s, 100s)
Gordon Boro-Packs: Aluminum sulfate 49% and calcium acetate 51% per packet (100s)
Pedi-Boro®: Aluminum sulfate 1191 mg and calcium acetate 839 mg per packet (12s, 100s)
DOSAGE FORMS: CONCISE
Powder, for topical solution:
Domeboro® [OTC]: Aluminum sulfate 1191 mg and calcium acetate 839 mg per packet (12s, 100s)
Gordon Boro-Packs: Aluminum sulfate 49% and calcium acetate 51% per packet (100s)
Pedi-Boro® [OTC]: Aluminum sulfate 1191 mg and calcium acetate 839 mg per packet (12s, 100s)
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — For external use only. Do not occlude dressing to prevent evaporation.
USE — Astringent wet dressing for relief of inflammatory conditions of the skin; reduce weeping that may occur in dermatitis
WARNINGS / PRECAUTIONS
Other warnings/precautions: Appropriate use: For external use only; avoid contact with eyes. Discontinue use if irritation occurs. OTC duration of therapy: Not for OTC use >7 days.
DRUG INTERACTIONS
Bisphosphonate Derivatives: Calcium Salts may decrease the absorption of Bisphosphonate Derivatives. Exceptions: Pamidronate; Zoledronic Acid. Risk D: Consider therapy modification
Calcium Channel Blockers: Calcium Salts may diminish the therapeutic effect of Calcium Channel Blockers. Risk C: Monitor therapy
CefTRIAXone: Calcium Salts (Intravenous) may enhance the adverse/toxic effect of CefTRIAXone. Ceftriaxone binds to calcium forming an insoluble precipitate. Management: Use of ceftriaxone with calcium-containing solutions within 48 hours of one another is contraindicated in neonates (28 days of age or younger). In older patients, flush lines with compatible fluid between administration. Risk D: Consider therapy modification
DOBUTamine: Calcium Salts may diminish the therapeutic effect of DOBUTamine. Risk C: Monitor therapy
Eltrombopag: Calcium Salts may decrease the serum concentration of Eltrombopag. Management: Separate administration of eltrombopag and any polyvalent cation (e.g., calcium-containing products) by at least 4 hours. Risk D: Consider therapy modification
Estramustine: Calcium Salts may decrease the absorption of Estramustine. Risk D: Consider therapy modification
Phosphate Supplements: Calcium Salts may decrease the absorption of Phosphate Supplements. Risk D: Consider therapy modification
Quinolone Antibiotics: Calcium Salts may decrease the absorption of Quinolone Antibiotics. Of concern only with oral administration of both agents. Exceptions: Moxifloxacin. Risk D: Consider therapy modification
Thiazide Diuretics: May decrease the excretion of Calcium Salts. Continued concomitant use can also result in metabolic alkalosis. Risk C: Monitor therapy
Thyroid Products: Calcium Salts may diminish the therapeutic effect of Thyroid Products. Management: Separate the doses of the thyroid product and the oral calcium supplement by at least 4 hours. Risk D: Consider therapy modification
Trientine: Calcium Salts may decrease the serum concentration of Trientine. Trientine may decrease the serum concentration of Calcium Salts. Risk D: Consider therapy modification
Subscribe to:
Posts (Atom)